CN102940653A - Bee pollen water extract buccal tablet for preventing and treating alcoholic fatty liver - Google Patents

Abstract

The invention relates to a bee pollen water extract buccal tablet for preventing and treating alcoholic fatty liver, relating to the technical field of a process for preparing a buccal tablet from plants, particularly from bee pollen water extracts. The bee pollen water extract buccal tablet mainly comprises freeze-dried powder of bee pollen water extracts, sorbitol, starch slurry, magnesium stearate and a menthol alcohol solution, wherein the bee pollen water extracts are prepared through a bee pollen water extraction method and have molecular weight being less than 5000. The bee pollen water extract buccal tablet disclosed by the invention has an obvious effect of preventing and treating the alcoholic fatty liver without side effect and is low in cost and simple and easy to prepare.

Description

The bee pollen water extract buccal tablet of control alcoholic fatty liver

Technical field

The present invention relates to from plant, particularly prepare the Technology field of buccal tablet from the bee pollen water extract.

Background technology

Through nearly 200,000,000 people of the WHO statistics long-term alcohol user of China, because the toxic action of ethanol causes liver injury, approximately 2/3 can develop into alcoholic liver disease (ALD) in the alcoholic, it comprises alcoholic liver injury, fatty liver (AFL), hepatitis, hepatic fibrosis and liver cirrhosis, it is the progressive process of order, pathogenesis is complicated, and Chinese medicine still can to the AFL therapeutic effect.Alcoholic liver disease is one of common clinically hepatopathy, mainly is the hepatic injury due to the long-term heavy drinking of patient.According to abroad studies, alcoholic liver disease is the Etiological that causes liver cirrhosis, and almost 50% liver cirrhosis patient has the custom of drinking for a long time.

In recent years, along with China's living standards of the people improve, life style and dietary habit change, and the alcoholic liver disease sickness rate obviously rises, and becomes the second largest hepatopathy that is only second to viral hepatitis, and gradually to womanlike, teenagerization development.Alcoholic liver disease has belonged to frequently-occurring disease and commonly encountered diseases clinically, so, the clinical research of alcoholic liver disease caused widely paid close attention to.The age of sending out well of alcoholic liver disease is 30-50 year, and its sickness rate increases year by year, and rejuvenation and tendency faggoty are arranged.Find that by research the patients with alcoholic liver disease age is larger, history of drinking history is longer, and drinking amount is larger, and liver function injury is just heavier; Alcoholic liver disease is except outside the Pass having with duration of alcohol consumption and drinking amount, and also closely related with the quality of class that the patient drinks and patient's alcohol drinking patterns, the drinks quality is poorer, and its prevalence is higher; Empty stomach drinking white spirit or drinking mixed multiple drinks, prevalence also can obviously increase; Secondly, although the male patient more than female patient, if the men and women drinks the wine of same amount, the women more easily suffers from alcoholic liver disease than the male, and clinical symptoms is serious than the male.Because be subjected to the impact from factors such as body quality, fat and gastric emptying times, women's alcoholic liver damage has high susceptibility.

Excessive drinking can cause organa parenchymatosum's blood capillary to change and steatosis, and then develops into atrophy and the sclerosis of organ, can appear at liver, lung, heart and brain at first; Obesity can make free fatty (FFAs) increase in the body, and the fat toxicity that the latter causes except itself, oxidation, the inhibition glycogen that also can suppress glucose synthesize, affect islet beta cell function, accelerate that triglyceride is accumulated etc. in hepatocyte.Ethanol and obesity can make outside above-mentioned all pathological changes increase the weight of, also can bring out fat hepatitis, and can promote active oxygen and 2-α-hydroxyethyl thiamine pyrophosphate-4-glycollic aldehyde base to produce and increase, make alcoholic fatty liver (ASH) and non-alcoholic fatty liver disease (NASH) all be in high-caliber oxidative stress status, impel inflammation and fibrosis constantly to upgrade.Abnormality of Glycolipid Metabolism and excessive drinking can also show the synergism to insulin resistant (IR), IR is an important symbol of fat and Overweight people metabolism syndrome, it simultaneously also is the sign that FFAs assembles at liver, FFAs in the hepatocyte can be used as the carrier of non-TG metabolite, accelerates disorganization and inflammatory infiltration and fibrosis; Ethanol can mediate peripheral IR and stimulate the liver fat acid metabolic, can also mediate oxidation of ethanol at ethanol dehydrogenase and become in the acetaldehyde process, because NAD ⁺Make NAD to the NADH conversion ⁺Consuming increases, and promotes FFAs synthetic, suppresses lipid and decomposes, and finally causes TG to accumulate in hepatocyte.In addition, cause obvious malnutrition different with weight loss from traditional alcohol user, carousing person may appetite increase, and more takes in the foods such as fiber, high fat, the additional energy that obtains in the ethanol can not be offset by reducing food intake dose, finally cause body weight to increase and obesity.

Under chronic excessive drinking, diabetes and fat condition, the gut permeability that mucosa injury causes strengthens, the giant molecule material such as the relevant molecule of pathogen that make intestinal bacteria decompose generation enter the enteral circulation, and advance people's liver by Portal system, activate hepatic stellate cell and express TLRs.Behind the TLRs ligand stimulation, fibroblast is activated the MAP signal pathway, activates NF-κ B, impels collagen muscle fiber archeocyte to secrete a large amount of proinflammatory cytokines and chemokines, makes blood vessel produce inflammatory reaction and fibrosis on every side.Especially tumor necrosis factor-alpha, interleukin-6, serum endotoxin/lipopolysaccharide and blood plasma collagen activation inhibitor-1 etc. can be used as the important biomolecule label that child NAFLD transforms to NASH.

Long-term excessive drinking can make hepatocyte generation steatosis, necrosis and regeneration, causes alcoholic liver disease (ALD); Main manifestations is three kinds of forms on histopathology: alcoholic fatty liver, alcoholic hepatitis and alcoholic cirrhosis, these three kinds of forms can also can be mixed existence separately.Along with living condition's improvement, excessive drinking has the trend of increasing.Because China's hepatopathy mainly causes by hepatitis virus, hepatitis virus carrier more may cover being actually ethanol as the hepatopathy of the cause of disease.Therefore, correctly be familiar with the hepatic injury that ethanol causes, in time diagnose and control has great importance.

According to the study, the cause of disease of alcoholic liver disease is the excessive absorption of ethanol, the ethanol of taking in mainly passes through simple diffusion absorption at duodenum and epimere ileum, stomach also can slowly absorb a small amount of ethanol, enter ethanol in the blood circulation along with blood flow spreads rapidly, reach very soon balance at more organs of vascularity such as liver, lung and brains.Ethanol can not store, must be by metabolism, liver is the main organ of alcohol metabolism in the body, wherein 90～95% carry out oxidative metabolism at liver by ethanol dehydrogenase (ADH) and microsome oxidation of ethanol enzyme system (MEOs), long-term heavy drinking is when increasing the weight of burden of liver, to a great extent to the liver injury.Primary product behind the alcohol metabolism is acetaldehyde, also produces simultaneously the oxidative stress product, and acetaldehyde is carbon dioxide and water by the final product of aldehyde dehydrogenase (ALDH) oxidative metabolism again subsequently.Alleviating alcohol addiction is one of crucial measure of ALD treatment, and alleviating alcohol addiction can obviously improve ALD patient's life quality.The abnormal liver function of ALD is taken a turn for the better rapidly, obviously improve survival rate; For slight ALD, can not continue development after the alleviating alcohol addiction; Liver cirrhosis fully forms, and portal hypertension and esophageal varicosis person are arranged, and alleviating alcohol addiction also is difficult to reverse, but can improve active process, the generation of complication.Patients with alcoholic liver disease merges heat/potein deficiency malnutrition usually, and malnutrition can aggravate alcoholic liver injury.Therefore, patients with alcoholic liver disease should be rich in the low fat soft diet of high-quality protein and vitamin(e) B group, high heat, and suitably replenishing in case of necessity branched-chain amino acid is main compound amino acid supplement.Serious alcoholic liver disease should be carried out and lie up, and the stabilization sub stage of disease should be done muscular training, and such as non-strenuous exercise, gymnastics, swimming, physical exercise simple in the family is effective equally.

At present, the definite mechanism of relevant alcoholic fatty liver is not yet fully clear; It is generally acknowledged drinks for a long time can make acetaldehyde growing amount increase in the body, and the balance of NADH/NAD changes and causes lipid metabolism and transhipment disorderly, and alcoholic fatty liver is to have weakened the metabolism of normal liver cell and the stability of liver plasma membrane owing to ethanol.1. ethanol intermediate product acetaldehyde and acetic acid can make the ratio of reducibility coenzyme I and codehydrogenase Ⅱ raise, thereby suppress the mitochondrion tricarboxylic acid cycle, make intrahepatic fat acid metabolic generation obstacle.2. ethanol has the effect that increases specifically the choline requirement, and the deficiency of phospholipid has affected the synthetic of lipoprotein, transports the generation obstacle thereby make.3. heavy drinking causes gastrointestinal dysfunction, affect the absorption of trace element, make vivo oxidation phosphorylation and fatty acid beta-oxidation impaired, the blood free fatty acid increases, promote fatty liver to form, ethanol stimulate adrenal gland and pituitary adrenal axis in a large number, increase the fatty tissue resolution ratio, make the synthetic increase of triglyceride and accumulation.4. drink for a long time and can induce the activity of Cytochrome P450 in the hepatomicrosome, it is active to increase and more increases the weight of ethanol and metabolite to the toxic action of liver.The mechanism more complicated of the hepatic injury that alcoholism causes except the direct toxic action of ethanol, in the alcohol metabolism process, produces a large amount of oxygen-derived free radicals, causes hepatic lipid peroxidation, is a reason that forms hepar damnification.

From prevention effect, alleviating alcohol addiction is extremely important to the treatment prognosis of alcoholic liver disease, and alleviating alcohol addiction is throughout one's life treatment, and only this item can change the hepatopathy process.Strengthen society and propagate and educate, change lifestyles, reduce strong ethanol consumption, early stage diagnosis and treatment alcoholic liver and improve alleviating alcohol addiction success rate etc., can gradually reduce the sickness rate of alcoholic liver disease.

Studies show that bicyclol has good function for protecting liver and reducing enzyme activity, obviously be better than the polyene phosphatidylcholine group from resume speed and the degree of ALT, AST, ALP and GGT, its mechanism may be polyphenoils glutathion in the inductor-s-transferring enzyme (GST) and reduced glutathion (GSH), improve the hepatocyte oxidation resistance, improve GSH level in the liver cell mitochondria, bicyclol can also be protected the hepatic mitochondria structure, resists all kinds of hepatic injury negative effects; Bicyclol is not inhibitor, but by removing oxygen-derived free radicals, and the protection liver plasma membrane makes liver cell nuclear DNA avoid damage and reduces apoptotic generation and play hepatoprotective effect; Bicyclol can alleviate the hepatic injury that lipid peroxidation that ethanol causes causes, thereby improves the inflammation necrosis, shows that bicyclol is a kind of better medicament selection for the treatment of alcoholic fatty liver.

Because fatty liver is not to be independent sexually transmitted disease (STD) kind, by causing the damage of liver function, cause the variation of blood parameters and enzyme value.In the test item of reaction hepatocyte injury, the most common with the sero-enzyme value, such as glutamate pyruvate transaminase (ALT), alkali phosphatase (ALP), lactic acid dehydrogenase (LDH) etc.When fatty the change occurs in liver, owing to hepatocyte suffers damage, cytopathy, necrosis, cell membrane fragmentation or membrane passage increase, and ALT contained in the hepatocyte will be released in the blood, makes the active increase of ALT in the blood.Because ALT mainly is present in the hepatocyte, when its often prompting that obviously raises has hepatic injury; When the fat change occured liver, it was main raising mainly with ALT.Glutamate pyruvate transaminase (ALT) is the main project of diagnosis hepatocyte material injury, and its height often parallels with state of an illness weight.

Someone likens into two locusts on rope of hyperlipemia to fatty liver and coronary heart disease because obesity, hyperlipemia, diabetes and excessive drinking be fatty liver commonly encountered diseases because of, and these factors are close with atherosclerosis and coronary heart disease too.Obvious myocardial damage and hemodynamics disturbance are arranged, the T cellular immune function decreased, the liver biopsy studies show that, 91.4% has hepatic cell fattydegeneration in these cases.Generally speaking, the ethanol fatty liver belongs to the reversibility disease, and early diagnosis and in time treatment often can recover normal.Long-term edible high lipid food or heavy drinking, ethanol can directly be poisoned hepatocyte, affects its structure and function; Many people are exactly because insobriety is just suffered from alcoholic hepatitis, fatty liver causes liver damage.And hepatic injury can cause triglyceride (TG) to descend, triglyceride is the fat molecule that long-chain fatty acid and glycerol form, be the maximum lipid of people's in-vivo content, most tissues all can utilize the triglyceride catabolite to supply with energy, is the main source of energy i (in vivo).The significant quantities of fat that fatty liver can cause eating absorbs minimizing, and bile secretion is not enough, can not decompose the fat of eating into, increases the weight of the state of an illness thereby fat forms fat drop at liver.

Bee pollen is the stamen that is gathered the sources of nectar and pollen by Apis, the dough of carrying back nest through processing, its nutritional labeling is very abundant, not only contains rich in protein, saccharide, lipid, vitamin, organic acid, mineral, nucleic acid, also contains enzyme and other biological active substance.Bee pollen is usually used in health food and nutraceutical, its chemical composition studied, so that the bee pollen product of the more kinds of exploitation, take full advantage of Bee Pollen Resource, be a current developing direction.Bee pollen is the elite of plant, is described as " the most completely nutriment ", " concentrated nutrition library ", is considered to the most promising food resource of 2nd 1 century.The medical care effect of bee pollen in recent years more and more by people cognition, but exist the material of one class preventing and control alcoholic fatty liver just not known in the bee pollen, study for many years this class material of discovery through us and in bee pollen, be water soluble state, thereby separation and Extraction is difficult especially.

The Bee Pollen Resource of China is very abundant, and output is large, and kind is many, but the bee pollen product is less, and the health product of declaring only have kind more than 20, and how the development of new functional food is very worth research and discussion.Yet research is also grasped the Changing Pattern of the crucial physical and chemical indexs such as protein, ash, moisture and Determination of Vitamin C of bee pollen, is still the focus of present research; Along with the increase of people to pollens nutrition product demand, the basic research of China's pollen and applied research will deepen continuously, and will give human more value of creating.In recent years, pollen has some progress at medicine, food, health food, cosmetic field; Such as, pollen treatment prostatitis, tumor, hepatitis, cardiovascular disease, and the pollen wet goods research of pollen polysaccharide Sulfation, pollen metabolism, pollen pharmaceutical carrier, pollen recombiant protein, pollen fermentation food, pollen antiseptic, SCF-CO 2, the exploitation of China's bee pollen has wide market.

Modern study proves, pollen polysaccharide can improve quantity and the function of body T lymphocyte and macrophage, improves seroimmunity Protein G level; the enhancing human body immunity function; thereby play tumor suppression and antitumaous effect, and can effectively stop radiotherapy, chemotherapy damage, protection body.The multiple Antioxidative Factors such as Flavonoid substances, polyphenol compound, carotenoid in the bee pollen can be worked in coordination with mutually the performance antioxidation; Bee pollen is with its efficient antioxidant activity, suffers from the disease relevant with radical damage and plays an important role aspect the defying age control is human; Therefore, bee pollen is the functional food that a kind of suitable ideal has antioxidation.Bee pollen nutrition is comprehensive, composition is extremely complicated, contain life required complete nutrients matter and various bioactivators, have and regulate immunologic function, growth promotion, resisting fatigue, anti-aging, vessel softening, blood fat reducing, the various biological functions such as short hemopoietic, beauty treatment and weight reducing, cellular immunization, humoral immunization all there are obvious potentiation, but utilize the bee pollen aspect research of relieving the effect of alcohol to remain blank.

Bee pollen is the dietotherapeutic pollen kind in the Chinese medicine treasure-house, as Chinese traditional medicine, the history of its dietotherapeutic has exceeded thousands of years, Shennong's Herbal before 2400, Compendium of Material Medica are all on the books to the Pharmacopoeia of the People's Republic of China of today, are regarded as " elixir " with its magical effect especially among the people.Find in pollen, also to exist a class to have the material that promotes alcohol metabolism through our up-to-date research, have remarkable effect to promoting the body aspect of relieving the effect of alcohol.

Present various dinner party is more and more, and the sickness rate of the various diseases that brings out owing to drinking improves year by year, and the healthy problem that excessive drinking is brought out has become affects modern's importance of quality of life.

Find also to exist in the bee pollen class to have the material that promotes alcohol metabolism through our up-to-date research, have remarkable effect to promoting body to relieve the effect of alcohol, prevent and treat the fatty liver aspect.Be that 201010607398.7 Chinese patent discloses by water extracting method such as number of patent application, bee pollen through breaking cellular wall, immersion, water extraction, ultrafiltration, is obtained the bee pollen water-soluble substances, and proof bee pollen water-soluble substances have the effect for the treatment of fatty liver.

Present various dinner party is more and more, and the sickness rate of the various diseases that brings out owing to drinking improves year by year, and the healthy problem that excessive drinking is brought out has become affects modern's importance of quality of life.

Buccal tablet, be a class without peptic digestion, directly absorb by oral mucosa and enter blood, adopt that soluble material carries out the tablet that coating is made for main coating material in the oral cavity.Can prevent acidity and enzyme to the destruction of some drugs or prevent that medicine is to the intense stimulus of stomach.

Summary of the invention

The object of the invention is to invent a kind of bee pollen water extract buccal tablet of energy high-efficiency prevention and control alcoholic fatty liver.

The present invention mainly is comprised of lyophilized powder, Sorbitol, starch slurry, magnesium stearate and the Mentholum alcoholic solution of the molecular weight of obtaining with the bee pollen water extracting method less than the bee pollen water extract of 5000D.

Described lyophilized powder, Sorbitol, starch slurry, magnesium stearate, and the Mentholum alcoholic solution accounts for respectively 50～85%, 5～25%, 5～25%, 0.1～1.0%, 0.1～0.4% of buccal tablet gross mass.

The present invention utilizes bee pollen water extract treatment alcoholic fatty liver effect remarkable, and has no side effect, and expense is cheap, and is simple.Bee pollen is the stamen that is gathered the sources of nectar and pollen by Apis, the dough of carrying back nest through processing, its nutritional labeling is very abundant, not only contains rich in protein, saccharide, lipid, vitamin, organic acid, mineral, nucleic acid, also contains enzyme and other biological active substance.The bee pollen water extract can be in the pharmacological action of gene level performance control alcoholic fatty liver, and the present invention's research has solved the molecule mechanism that the alcoholic strength fatty liver is separated in its control substantially, for this reason, files an application patent of the present invention.

Confirm after research and testing; finding has many bioactive substances under one's belt easily by stomach acids destroy in the bee pollen; and can directly absorb by hypoglossis mucous membrane, can protect better bioactive substance to exempt from destruction so make buccal tablet, improve the result of use of product.Also absorbed a large amount of food in the time of through our finder's heavy drinking of research, particularly high innage fat food makes people's stomach be high full abdomen state, the emptying general needs of its stomach are about 2 hours, if take simultaneously antialcoholic drugs, because comparing with stomach, dose differs too great disparity, be difficult to play a role and lost efficacy, if but adopt heavy dose of antialcoholic drugs, can be subject to the restriction of gastric capacity again and can't implement, so the antialcoholic drugs that uses after meal preferably adopts the mode without stomach, Here it is, and why we will develop the main cause of buccal tablet.

Description of drawings

Fig. 1 is natural health matched group liver tissue slices figure.

Fig. 2 is natural health matched group renal tissue slice map.

Fig. 3 is alcoholic fatty liver model group liver tissue slices figure.

Fig. 4 is alcoholic fatty liver model group renal tissue slice map.

Fig. 5 is gavage buccal tablet group liver tissue slices figure.

Fig. 6 is gavage buccal tablet group renal tissue slice map.

The specific embodiment

The so-called bee pollen of the present invention refers to pass through the pollen that Apis is gathered such as Flos Camelliae Japonicae powder, Pollen Brassicae campestris, Flos Nelumbinis pollen etc.

One, preparation bee pollen control alcoholic fatty liver water extract lyophilized powder:

1, bee pollen remove impurity, drying make water content drop to 4～8%.

2, adopt the mode of comminution by gas stream breaking cellular wall with broken wall of melissa pollen.

3, soak the bee pollen of breaking cellular wall with the normal pressure and temperature pure water, processed 10～40 minutes with low-frequency ultrasonic waves simultaneously, the temperature of control supersound extraction liquid is at 10～40 ℃.

4, turn refrigerated centrifugation with 8000～15000 and remove solid impurity, get supernatant.

5, with described supernatant under 1～5 ℃ ambient temperature with 5000D molecular sieve ultra-filtration and separation, obtain molecular weight and be the following bee pollen water-soluble substances of 5000D.

6, above-mentioned bee pollen water extract lyophilization 24～48 hours preparation water content is lower than the lyophilized powder of 6% bee pollen water extract.

Two, preparation buccal tablet of the present invention:

1, granulating process: after the boiling pot is preheating to 40～60 ℃, first freeze-dried bee pollen, Sorbitol, starch slurry are added in the boiling pot, arrange according to the following table parameter, open peristaltic pump spray purified water and carry out one-step palletizing.Granulate and finish rear magnesium stearate and the Mentholum alcoholic solution mix homogeneously of adding, sub-cooled prepares the buccal tablet of the bee pollen water extract that relieves the effect of alcohol again.

Typical several quality proportioning table: (unit: kg)

?	Lyophilized powder	Sorbitol	Starch slurry	Mentholum solution	Magnesium stearate
						Proportioning 1	75	9	15.5	0.1	0.4
Proportioning 2	80	8	11.5	0.2	0.3
						Proportioning 3	84	8	7.4	0.3	0.3

Processing parameter:

Parameter	Inlet temperature	Leaving air temp	The air inducing frequency	Peristaltic pump	Atomizing pressure
						During whitewashing	60-80℃	40-55℃	40Hz	150rpm	0.2MPa
After the whitewashing	65-80℃	50-60℃	35Hz	150rpm	0.2MPa

2, tablet forming technique: adopt ZP1100 tablet machine (29 punching) to carry out tabletting experiment, technological parameter: 30～40 rev/mins of rotating speeds; Operating pressure 7～15kN; Sheet weighs 0.4～0.6g.

Three, use:

(1) subjects:

The Wistar cleaning level male rat in ages in gavage 22 week, body weight 344.43 ± 38.49; Nature control rats every day is by body weight 1% gavage pure water; Model group rat every day is by body weight 0.5% gavage strong, colourless liquor distilled from sorghum and body weight 0.5% gavage Adeps Sus domestica simulation; Gavage buccal tablet experimental group rat every day by body weight 0.5% gavage strong, colourless liquor distilled from sorghum and body weight 0.5% gavage Adeps Sus domestica after 8 hours gavage buccal tablets.

(2) experimental group adopts the mode of empty stomach gavage buccal tablet of the present invention to test:

Using dosage: by the amount gavage of every rat 50-100mg every day buccal tablet of the present invention, connect and took 30～40 days.

(3) comparing result:

1, rats in test groups liver and renal tissue section result is relatively:

(1) with natural health matched group liver and renal tissue section, sees Fig. 1,2.

Be polygon from Fig. 1,2 visible male white rat liver hepatocyte clear in structure, hepatic sinusoid is obvious, and the hepatic cords marshalling does not have obvious fat vacuole in the hepatocyte; Kidney group section mesonephric glomerulus structure is clear complete, and the glomerular capsule gap is obvious, moderate, not obviously damage.

(2) with gavage Chinese liquor Adeps Sus domestica model group liver and renal tissue section, see Fig. 3,4.

From Fig. 3,4 visible hepatocyte obscure boundaries, becoming in the circle has cavity, and the hepatic sinusoid pressurized narrows down, and liver rope arrangement disorder has the fibrosis sign; The glomerule structure is unclear, and damage is serious, the glomerular capsule distortion.

(3) Fig. 5,6 is seen in gavage buccal tablet liver of the present invention and renal tissue section.

From Fig. 5,6 visible liver lobules of liver clear in structure, hepatic sinusoid is evenly distributed, and hepatocyte is polygon, marshalling; The renal glomerulus structure is obviously improved, and the glomerular capsule gap is obvious, has the vestige of obvious glomerule reparation.

From section, find to indulge in excessive drinking except liver is caused the major injury for a long time, also can cause serious damage to kidney, but all there is good prevention effect in buccal tablet of the present invention to liver and the kidney that damages.

2, on an empty stomach after the gavage buccal tablet intervention of the present invention to the comparative analysis of rats in test groups Main Blood Biochemical Index.

Adopt the blood sampling of anesthesia ventral aorta, detect Main Blood Biochemical Index by Toshiba's fully automatic blood bio-chemical detector after getting serum.Comparative analysis such as following table:

Group	Naturally organize	Model group	Gavage tea extract
				ALT	73.0±16.67	81.8±14.81	36.4±8.88
ALP	102.50±11.90	179.40±32.39	94.40±16.20
				GRE	55.78±2.97	48.02±4.44	54.18±2.05
LDH	962.75±96.05	722.20±271.52	1381.60±338.38
				CHO	1.23±0.08	1.57±0.18	1.09±0.11
TG	1.25±0.18	1.46±0.31	1.13±0.14
				BUN	5.89±0.65	4.77±0.36	3.75±0.27

Through the SPSS statistics, natural matched group and model group ALT and gavage Flos Camelliae Japonicae powder water extraction liquid buccal tablet group difference are extremely remarkable; The transaminase extensively exists in the histiocyte, and especially the strongest with activity in the tissue such as liver, cardiac muscle, brain, kidney, plasma content is very low when normal, and ALT mainly is present in liver, and ALT is released in a large number blood and can causes that the transaminase raises in the blood when the hepatic tissue disease damage.This experiment gavage buccal tablet group serum transaminase vigor is very low, illustrates that buccal tablet is very strong to the repair effect of liver.

Healthy Human Serum ALP is mainly from liver and skeleton, and the ALP in the liver is with the transhipment of material and drain relevant.And the type 2 diabetes mellitus patient also causes the obstacle of lipid metabolism to reach at intrahepatic deposition simultaneously because insulin secretion obstacle or insulin resistant cause metabolism obstacles of blood glucose, even forms fatty liver, and makes liver damage cause the rising of serum levels of ALP level.Model group alkali phosphatase and other two experimental grouies difference are extremely remarkable; Illustrate that the Flos Camelliae Japonicae powder buccal tablet can improve hepatocyte injury, reduce the alkaline phosphatase enzyme level, rising and the hepatocellular damage of alkali phosphatase (ALP) are closely related, illustrate that the excessive drinking of this experimental model group and high fat diet are very serious to the hepatocyte injury, and can improve the untoward reaction that long-term excessive drinking and high fat diet cause behind the gavage buccal tablet, repair the liver of damage.

Add up through SPSS, model group creatinine (GRE) is extremely remarkable with natural matched group difference, with gavage buccal tablet group of the present invention significant difference, illustrate that the also high fat diet meeting of indulging in excessive drinking under this experiment condition descends the utilization of body exogenous protein, and gavage buccal tablet of the present invention can improve the utilization of body exogenous protein.

Through the SPSS statistics, model group lactic acid dehydrogenase (LDH) is extremely remarkable with gavage buccal tablet group of the present invention difference; Lactic acid dehydrogenase is glucolytic key enzyme, the lactic dehydrogenase enzyme level is very high behind the gavage bee pollen buccal tablet, illustrate and promote glycolysis closely related, that is to say that buccal tablet of the present invention has stronger short glycolysis under this experiment condition, be beneficial to that liver relieves the effect of alcohol and carbohydrate metabolism.

Type 2 diabetes mellitus is the class disease take insulin resistant and islet beta cell function obstacle as principal character, and wherein losing with dysfunction of beta Cell of islet plays a decisive role in the generation of disease and development.Studies show that in recent years, cholesterol metabolism and islet beta cell function are closely related.Under normal circumstances, absorption and outflow that beta Cell of islet can be controlled the cell inner cholesterol by series of receptors and the transport molecule of its surface expression are so that the content of cell inner cholesterol maintains a dynamic equilibrium.After the metabolism of beta Cell of islet inner cholesterol gets muddled, can affect by number of ways the carbohydrate metabolism of β cell, finally induce islet beta-cell apoptosis.Therefore, the cholesterol metabolism disorder may be a new mechanism that causes type 2 diabetes mellitus patient β cell dysfunction.Through the SPSS statistics, model group cholesterol (CHO) is extremely remarkable with other two experimental group differences, illustrate that excessive drinking and high fat diet are the arch-criminals who causes hypercholesterolemia, and gavage buccal tablet of the present invention has remarkable hypercholesterolemia effect.

Fat toxicity due to the high triglyceride (HTG) has caused extensive concern in recent years, and it can cause and increase the weight of insulin resistant (IR), and the biological effect of insulin is reduced.Glycogen is synthetic by participating in for liver, glycogenolysis and glyconeogenesis play a part direct and important in keeping glucostasis, particularly G-6-Pase plays a crucial role in glycogen generates, it is unusual that hepatic insulin resistance also shows as lipid metabolism, and discharging such as triglyceride increases and the liver steatosis.Through SPSS statistics, model group triglyceride (TG) and natural matched group and gavage buccal tablet group of the present invention significant difference; From the experiment situation, serum high triglyceride level appears in model group, illustrates that long-term excessive drinking and high fat diet are the main causes that produces hypertriglyceridemia, is one of paathogenic factor of bringing out type 2 diabetes mellitus; And take buccal tablet of the present invention to the Triglyceride Metabolism of Induced by High Fat Diet has good regulating and controlling effect owing to indulging in excessive drinking also.

Nature matched group BUN and other experimental group difference are extremely remarkable; Model group BUN is with to take buccal tablet difference of the present invention extremely remarkable.We the high fat diet of indulging in excessive drinking for a long time cause the degradation of feed intake experiment prompting, the availability degradation that causes body exogenous protein, to cause experimental group serum urea nitrogen level main cause on the low side, and promoting body to the availability of protein behind the gavage buccal tablet of the present invention, metabolite obviously reduces.

Above result shows: buccal tablet of the present invention is to having sizable therapeutical effect because the rat liver fat that excessive drinking and high fat diet cause becomes, and from blood parameters and liver tissue slices, the improvement effect of buccal tablet of the present invention is very clear and definite.

3, after the buccal tablet intervention of the present invention major gene in the alcoholic fatty liver rats in test groups liver metabolism express is changed comparative analysis, such as following table:

Find by biochip technology research the important metabolic pathway of many impacts in the model group rat liver expressing gene of long-term excessive drinking and high fat diet (such as with the related gene that relieves the effect of alcohol, Genes Associated with Lipid Metabolism, hepar damnification reparation gene) expression of key gene all shows the situation that is unfavorable for the body homergy, and the variation of this gene expression has obtained good correction after the intervention of gavage buccal tablet, we are not difficult to find that the ability that this being similar to " error correction " expressed is just embodying the liver metabolism obstacle of gavage buccal tablet to forming owing to for a long time excessive drinking and high fat diet from lower example table, the reparation of liver organization damage has very strong improvement effect, research by us finds that from gene level the gavage buccal tablet can relieve the effect of alcohol effectively, improve the metabolism of liver, the generation of control alcoholic fatty liver.

3.1 the impact of behind the gavage buccal tablet key gene relevant with lipid metabolism in the alcoholic fatty liver being expressed

Group

Adh4

Adh6

Fasn

Pklr

LpL

Scd

Scd1

Model group/naturally organize

↓2.05

↓264

↑4.17

↑3.53

↓3.12

↑6.76

↑6.47

Buccal tablet group/model group

↑2.33

↑29.68

↓5.15

↓3.4

↑5.42

↓6.81

↓6.17

Annotate: in the upper table ↓ 2.05 times of the expression ratio downward modulations of 2.05 expression Adh4 genes model group and natural matched group in hepatocyte mRNA, 2.33 times of the expression ratio rises of ↑ 2.33 expression Adh4 gene gavage buccal tablet groups and model group.

3.1.1 Adh4: alcoholdehydrogenase 4, participate in alcohol metabolism and aldehyde metabolism, oxidation of ethanol is decomposed.It just works when the ethanol high concentration, and is different from other Adh on the immunology, and different substrate specificities is arranged.Adh4 also participates in the metabolism of retinol, has the physiological action of obvious degradation epinephrine and norepinephrine.

This experiment condition drag group and natural matched group ratio, alcoholdehydrogenase 4(Adh4) down-regulated expression of gene 2.05 times, illustrate: the model group of long-term excessive drinking and high fat diet has been reduced alcoholdehydrogenase 4 genes, the expression that reduces this enzyme just means that the model group downward modulation is by the approach of ethanol dehydrogenase system decomposition ethanol, liver is descended by the ethanol dehydrogenase system function of relieving the effect of alcohol, and is the one of the main reasons that causes rat hepatocytes alcohol metabolism obstacle.

Under this experiment condition experimental group with the buccal tablet intervention after with alcoholic fatty liver model group ratio, alcoholdehydrogenase 4(Adh4) up-regulated 2.33 times, illustrate: buccal tablet of the present invention can pass through to raise alcoholdehydrogenase 4(Adh4) gene expression, recover hepatocyte by the function of relieving the effect of alcohol of alcohol dehydrogenase enzyme system, reaching and improve the purpose of relieving the effect of alcohol, is that buccal tablet of the present invention has one of the effect reason of significantly relieving the effect of alcohol.

3.1.2 Adh6: alcoholdehydrogenase 6, participate in the oxidation of ethanol metabolism, transcribing of this gene arranged in the harmonization of the stomach liver, be main alcohol metabolism enzyme in the rat hepatocytes, participate in one of enzyme of present most study in the process of relieving the effect of alcohol.

This experiment condition drag group and natural matched group ratio, alcoholdehydrogenase 6(Adh6) down-regulated expression of gene 264 times, illustrate: model group has seriously been reduced the approach by ethanol dehydrogenase system decomposition ethanol, meaning that long-term excessive drinking and high fat diet meeting make liver significantly descend by the ethanol dehydrogenase system function of relieving the effect of alcohol, is the one of the main reasons that causes rat hepatocytes alcohol metabolism obstacle.

Under this experiment condition experimental group with the buccal tablet intervention after with alcoholic fatty liver model group ratio, alcoholdehydrogenase 6(Adh6) up-regulated 29.68 times, illustrate: buccal tablet of the present invention can significantly raise alcoholdehydrogenase 6(Adh6) gene expression, be that buccal tablet promotes one of reason that the ability of relieving the effect of alcohol improves, have positive effect to relieving the effect of alcohol and preventing and treating alcoholic fatty liver.

3.1.3 Fasn: fatty acid synthetase participates in fatty acid biological synthetic.In the mammal, fatty acid synthetase plays vital effect in fatty acid is synthetic, be responsible for all catalytic steps of S-acetyl-coenzyme-A and a kind of long-chain palmitic acid of malonyl coenzyme A de novo synthesis (cetylate), the expression of gene directly affects the fatty acid synthetase number control body fat deposition is had great importance.

This experiment condition drag group leader's phase indulges in excessive drinking and high fat diet makes in the hepatocyte fatty acid synthetase gene and natural matched group than 4.17 times of up-regulateds, illustrate: it is the arch-criminal who causes hepatocyte fat excess deposition that model group can make synthetic the increasing of fatty acid synthetase, causes fatty liver generation primary factor.

5.15 times of the gene expressions of gavage buccal tablet group and model group downward modulation fatty acid synthetase under this experiment condition illustrates: the buccal tablet group can reduce the hepatic tissue fatty acid synthetic by reducing the synthetic of fatty acid synthetase, and is significant to alleviating the liver fat change.

3.1.4 Pklr: pyruvate kinase, involved in sugar zymolysis in the liver.

This experiment condition drag group leader's phase indulges in excessive drinking and makes that pyruvate kinase gene and natural matched group illustrate than 3.53 times of up-regulateds in the hepatocyte: model group is by raising this gene, sees that from the organism metabolism angle strengthening glycolysis means exactly and promoted lipidosis.

Gavage buccal tablet group and 3.4 times of model group ratio downward modulation pyruvate kinase gene expressions under this experiment condition, illustrate: the enteric coatel tablets group can reduce hepatocellular glycolysis by downward modulation pyruvate kinase gene, hepatocyte is strengthened lipid metabolism favourable.

3.1.5 LpL: lipoprotein lipase, participate in fatty acid metabolism, be one of lipometabolic key enzyme.LpL is synthetic at the rough endoplasmic reticulum of parenchyma, and new synthetic LpL non-activity after glycosylation, just changes into active LpL.The heparin sulfate glycoprotein that is present in the cell membrane outer surface makes enzyme keep a kind of unvital enrichment stage, stimulated the LpL that obtains activating in the rear blood plasma by heparin, be distributed in the lipoprotein that contains triacylglycerol, it mainly is the triacylglycerol that decomposes Chylomicron and very low density lipoprotein (VLDL), and combination and being attached in these remnant lipoproteins, may absorb as liver the signal of these granules.LpL acts on lipoprotein, mainly decomposes the triacylglycerol in the lipoprotein, is to remove the rate-limiting enzyme of triacylglycerol in the blood plasma, and impels lipoprotein to shift cholesterol, phospholipid and apolipoprotein.LpL also has to be increased Chylomicron and is attached to ability on the LP receptor, promotes the Chylomicron picked-up.

This experiment condition drag group and 3.12 times of natural matched group ratio downward modulation lipoprotein lipase gene expressions, illustrate: model group can make the lipoprotein lipase content decrease, causes triacylglycerol to decompose and reduces, the change of acceleration model group rat liver fat.

Gavage buccal tablet group and model group illustrate than 5.42 times of up-regulateds under this experiment condition: the buccal tablet group can make that lipoprotein lipase is synthetic in the experimental group rat hepatocytes increases, and is conducive to hepatocyte and reduces fat, and alleviates liver fat and becomes.

3.1.6 Scd: sterin coenzyme A desaturase participates in fatty acid biological synthetic.Stearyl-coenzyme A desaturase (SCD) can be introduced in fatty acid carbon chain cis-9 position two keys, is catalysis butterfat cis-9, trans-11CLA and trans-7, the key enzyme that cis-9 CLA is synthetic.

3.1.7 Scd1: sterin coenzyme A desaturase 1 participates in fatty acid biological synthetic.Stearyl-coenzyme A desaturase 1 (Scd-1) is the biosynthetic rate-limiting enzyme of monounsaturated fatty acid, plays the center adjustment effect in fatty acid metabolism, also is one of genes of interest of leptin (Leptin) effect.Leptin and diabetes, obesity, fatty liver close relation are one of hot fields of in recent years metabolic disease.The type 2 diabetes mellitus patient, usually with insulin resistant, hyperleptinaemia, approximately there is fatty liver in 50% type 2 diabetes mellitus patient simultaneously.Scd-the 1st, the key enzyme that the catalysis satisfied fatty acid changes to monounsaturated fatty acid, closely related with generation, the development of a series of metabolism syndromes such as obesity, fatty hepatic lesions and insulin resistant, thereby the expression of research Scd-1, regulation and control may provide a very important lab index for the diagnosis of clinical disorders of lipid metabolism relevant disease and the monitoring of therapeutic effect, has broad application prospects in clinical medicine.Because Scd-1 mainly is present in endoplasmic reticulum, at present the detection of Scd in the body-1 is mainly adopted and measured blood fat index of unsaturation (unsaturated fatty acid/satisfied fatty acid ratio) or by molecular biology method Scd in the cell-1mRNA expression is detected.In sum, Scd-1 has play a part important in energy metabolism.By the research to Scd-1 and energy metabolism relation, can the mechanism of clearer understanding Scd-1 in energy metabolism, thereby be clinical targeting adjusting energy metabolism and avoid fat toxicity, a series of metabolic syndromes such as prevention or treatment are fat, fatty hepatic lesions and diabetes provide basic.

The model group of long-term excessive drinking and high fat diet raises 6.76 times of sterin coenzyme A desaturase (Scd) gene expressions with natural matched group ratio under this experiment condition, sterin coenzyme A desaturase 1(SCD-1) raises 6.47 times, illustrate: the two gene up-regulated is one of main molecule mechanism that causes the alcohol fatty change, what prevent and treat alcoholic fatty liver is the pathological index of most critical in the process of relieving the effect of alcohol, the processing mode effectiveness just is whether can control fatty liver, model group has raised two gene, and serious fatty liver has appearred in model group liver section display model group rat, even reaches the state of hepatic fibrosis.

Gavage buccal tablet group and 6.81 times of model group ratio downward modulation sterin coenzyme A desaturase (Scd) gene expressions under this experiment condition, downward modulation sterin coenzyme A desaturase 1(Scd-1) gene expression is 6.17 times, illustrate: the buccal tablet group has significant improvement effect to the formed alcoholic fatty liver of the bad habit of long-term excessive drinking and high fat diet, and consistent with the result of liver section, this change is one of main molecule mechanism of bee pollen buccal tablet control alcoholic fatty liver.

3.2 the impact of behind the gavage buccal tablet key gene relevant with hepatic injury, reparation and metabolism in the liver being expressed

Group	Cd2	Cd70	Il7r	Pla2g2a	Tnfrsf10b
						Model group/naturally organize	↑29.6	↑4.35	↓2.76	↓2.47	↑4.14
Buccal tablet group/model group	↓48.7	↓6.17	↑4.58	↑10.61	↓2.94

Annotate: in the table, 48.7 times of the expression ratio downward modulations of ↓ 48.7 expression Cd2 genes buccal tablet group and model group in hepatocyte mRNA, 29.6 times of the expression ratio rises of ↑ 29.6 expression Cd2 genetic model groups and natural matched group.

3.2.1 the Cd2:Cd2 molecule, receptor, protein binding participates in the Lipid Rafts polar, the guiding apoptosis, cell surface receptor connects signal transduction, cell attachment, natural killer cell activates, and is just regulating and control dendritic cell-stimulating, t cell activation, modulating T cell differentiation.Lipid Rafts refers to that the membrane lipid bilayer contains the microcell of special lipid and protein, and diameter is about 50～350nm, and microcell caves in and can form vesicle (caveola or alveole), and Lipid Rafts does not exist only on the cytoplasma membrane, and has on the Golgi membrane yet.Different Lipid Rafts have separately specific protein, and contained lipid is also incomplete same, and different functions is arranged.Lipid Rafts is comprised of sphingomyelins, ganglioside and cholesterol, because sphingomyelins contains chain saturated fatty acids, interact into a kind of orderly lipid phase with cholesterol, (Tm) is higher for its phase transition temperature, the flowability of adipose membrane is reduced and the stability increase, more unsaturated fatty acid is contained in film district around the Lipid Rafts, and the Tm temperature is lower, and phase-splitting has just appearred in the Lipid Rafts district of film and non-Lipid Rafts district like this.The function of dendritic cell in human body just is equivalent to a precaution device, and they find external invader's (antigen) from virus, antibacterial or other organs as the hardcore in the human immunocyte system, and information then gives a warning.They shake antigen as a kind of signal, make the T cell can enter timely and disperse the invader.

This experiment condition drag group raises 29.6 times of Cd2 genes with natural matched group than model group, illustrate: model group activates dendritic cell by raising the Cd2 gene, impels the immunocyte excessive activation, cause excessive immunoreation, bring out hepatocyte inflammation and fibrosis.

Buccal tablet group and 48.7 times of model group ratio downward modulation Cd2 genes under this experiment condition illustrate: can be by downward modulation Cd2 gene expression after buccal tablet is intervened, and alleviation immunocyte excessive activation prevents because hepatocyte inflammation and fibrosis are brought out in excessive immunoreation.

3.2.2 Cd70: be the CD27 part, belong to tumor necrosis factor-tumor necrosis factor receptor super family, be a pair of costimulatory molecules, in the activation of T, B, NK cell, propagation, play an important role, and CD27 can accurately regulate the degree of immunne response and the time that continues by CD70.Cd70 is a kind of II type transmembrane glycoprotein in the tnf family cytokines, when the recent application biochip technology detects renal carcinoma tissue and normal kidney tissue differential expression, finds Cd70 remarkable high expressed in renal carcinoma.

This experiment condition drag group raises 4.35 times of Cd70 gene expressions with natural matched group than model group, illustrates: model group improves hepatocyte immunne response level by raising Cd70 gene expression, promotes inflammation reaction and progression of fibrosis.

Buccal tablet group and 6.17 times of model group ratio downward modulation Cd70 genes under this experiment condition illustrate: can reduce the immunne response level by downward modulation Cd2 gene expression after buccal tablet is intervened, prevent because hepatocyte inflammation and fibrosis are brought out in excessive immunoreation.

3.2.3 Il7r: interleukin-17, receptor participates in the regulating DNA restructuring, immunne response, the cell surface receptor signal connects conduction, antimicrobial humoral response.

This experiment condition drag group has been reduced 2.76 times of interleukin-17 genes with natural matched group than model group, illustrate: the model group rat is because long-term excessive drinking and high fat diet meeting cause hepatocyte immunne response level to rise, expression by downward modulation interleukin-17 gene, increase the weight of hepatocellular inflammatory reaction, promote hepatocyte fat to become and Fibrotic process.

The buccal tablet group raises 4.58 times of interleukin-17 genes with the model group ratio under this experiment condition, illustrate: after buccal tablet is intervened, by raising the expression of interleukin-17 gene, anti-hepatocellular immunne response, alleviate the inflammation reaction, control alcoholic fatty liver and fibrosis are had positive effect.

3.2.4 Pla2g2a: phospholipase A2, basic 2A, calcium relies on, and participates in fat catabolism.

This experiment condition drag group and natural matched group ratio, the down-regulated expression of Pla2g2a gene 2.47 times, illustrate: long-term excessive drinking and high fat diet reduce the catabolism to fat in the hepatocyte, the process of weight fat liver by the expression of downward modulation Pla2g2a gene.

Alcoholic fatty liver model group ratio with experimental group rat after the buccal tablet intervention of the present invention and before intervening under this experiment condition, the up-regulated of Pla2g2a gene 10.61 times, illustrate: buccal tablet of the present invention is by having raised the expression of this gene, promote the catabolism of fat in the hepatocyte, favourable to the control alcoholic fatty liver.

3.2.5 Tnfrsf10b: Tumor Necrosis Factor Receptors surpasses family, member 10b, and Guang winter enzyme activity factor, the TRAIL combination participates in Guang winter enzyme and activates, and signal transduction activates NF-κ B guiding kinases, and the regulating cell apoptosis is just being regulated and control NF-κ B cascade.

This experiment condition drag group and natural matched group ratio, the up-regulated of Tnfrsf10b gene 4.14 times, illustrate: model group activates NF-κ B cascade by the expression of raising the Tnfrsf10b gene, promotes hepatocyte lipid peroxidation and inflammatory reaction, increases the weight of liver fat and becomes and fibrosis.

Alcoholic fatty liver model group ratio with experimental group after the buccal tablet intervention and before intervening under this experiment condition; the down-regulated expression of Tnfrsf10b gene 2.94 times; illustrate: buccal tablet of the present invention can be by downward modulation Tnfrsf10b gene expression; suppress the activation of NF-κ B in the rat hepatocytes; alleviate lipid peroxidation and inflammatory reaction, realize the target of protection hepatic tissue.

3.3 the impact of after the buccal tablet intervention key gene relevant with the control normal activity in the liver being expressed

Group	Fabp4	Hspb1	Igfbp6	Srd5a1
					Models of Fatty Liver group/naturally organize	↓5.64	↓2.65	↓3.97	↑2.6
Buccal tablet group/model group	↑4.86	↑3.16	↑6.65	↓2.72

3.3.1 Fabp4: FABP4 participates in the fat transportation.Fabp4 is the depots of mammal triglyceride, Fabp4 expresses with active and significantly strengthens in the Adipocyte Differentiation process, in triglyceride formation and steatolysis process, Fabp4 stores or discharges abundant fatty acid, participates in the biochemistry circulation of the generation of regulation and control triglyceride and dissolving.Reduce this gene expression meeting and cause fatty acid transportation obstacle in the hepatocyte, a large amount of synthetic fatty acids transport the hepatocyte ability and descend, and bring out fatty liver.Form in the experiment at rat nonalcoholic fatty liver, use High-fat diet, the mRNA of L-Fabp and protein expression enhancing in the rat liver expressed the most obvious during to 2 week when all to l2; Illustrate that high fat diet causes that at first it is a kind of adaptation response that L-Fabp express to strengthen, strengthen along with L-Fabp expresses further, cause fatty acid metabolism unbalance and cause that fatty liver occurs.Therefore, Fabps is expected to become the novel targets of the metabolic diseases such as treatment fatty liver, obesity, diabetes.

This experiment condition drag group and natural matched group ratio, the down-regulated expression of Fabp4 gene 5.64 times, illustrate: model group is by the expression of downward modulation Fabp4 gene, reduces that triglyceride generates and the biochemistry circulation of dissolving, promotes the generation that lipidosis and fat become.

Alcoholic fatty liver model group ratio with experimental group after the buccal tablet intervention and before intervening under this experiment condition, 4.86 times of the up-regulateds of Fabp4 gene, illustrate: after buccal tablet is intervened, by raising the expression of Fabp4 gene, promote abundant fatty acid to discharge, the regulation and control triglyceride generates and the biochemistry of dissolving circulates, and promotes the catabolism of fatty acid, and is significant to alleviating fatty liver.

3.3.2 Hspb1: many studies show that no matter body is in stress state or normal physiological state, all can participate in complicated and important biological process.Interact such as sHSP and other albumen, stop unnecessary interaction between albumen, keep various cell proteins stable; Carry out the maintenance of film, and relevant with the flowability of film fat; Have driving functions in the nuclear, or the Molecular regulator process, or protected protein; The stabilized cell skeleton participates in regulating growth and the differentiation of cell, suppresses the apoptosis of cell; Also have the functions such as immunology; In the pathophysiological process of the physiological status of keeping body and some disease, all play a significant role.

This experiment condition drag group and natural matched group ratio, the down-regulated expression of Hspb1 gene 2.65 times, illustrate: model group descends to damaging the hepatocellular ability of maintenance by the expression of downward modulation Hspb1 gene, is unfavorable for hepatocellular reparation.

Alcoholic fatty liver model group ratio with experimental group after the buccal tablet intervention and before intervening under this experiment condition, 3.16 times of the up-regulateds of Hspb1 gene, illustrate: after buccal tablet is intervened, improve the hepatocellular ability of maintenance by the expression of raising the Hspb1 gene, promote hepatocellular reparation.

3.3.3 Igfbp6: IGFBP (insulin-like growth factor binding protein) 6, regulating cell growth, signal transduction, negative regulation cell proliferation.Rise is conducive to Igf1 and plays a role, and control fatty liver and hepatic fibrosis are had fine effect.

Research confirms, and the formation of IGFs and hepatic fibrosis, liver cirrhosis develops relevant.Having isolated at present two kinds of IGFs is IGF-l and IGF-2.They act on target organ with autocrine, paracrine and endocrine mode.Nearly all endocrine IGF-l or IGF-2 all form relative molecular mass with insulin-like growth factor binding protein (IGFBPs) in body fluid be the complex of 150kb or 50kb.The single chain polypeptide that IGF-l is comprised of 70 amino acid residues, mainly synthetic at liver, be the extensive cell mitogen that exists of body and the promoter of differentiation and maturation, affect the adjusting of growth, differentiation and the metabolism of many organ inner cells.The above-mentioned functions of IGF-l is by IGF-l receptor (IGF-lR) mediation, and the effectiveness that IGF-l is combined with IGF-lR is subjected to the adjusting of IGFBPs.Liu Lixins etc. studies show that, IGFBP (insulin-like growth factor binding protein) 6 (IGFBP6) is expressed obviously in IGF-β l induces the HSC-T6 of activation and strengthened, and prompting IGF and receptor thereof participate in the formation of hepatic fibrosis.Because IGFBPs and IGFs have high-affinity and can regulate the biological activity of IGFs, these protein-bonded genesis of inducing generation also can affect hepatic fibrosis.Yet there are some researches show in addition, IGF-1 has the effect of anti-hepatic fibrosis in the body, can suppress the activation of HSC, its may with improve superoxide dismutase and catalatic activity, improve the ability that hepatocyte is removed free radical, the stimulating factor of minimizing HS activation etc. are relevant.

This experiment condition drag group has been reduced 3.97 times of IGFBP (insulin-like growth factor binding protein) 6 genes with natural matched group than model group rat, illustrate: model group has promoted hepatocyte fat to become and fibrosis by the expression of downward modulation IGFBP (insulin-like growth factor binding protein) 6 gene.

The buccal tablet group raises 6.65 times of IGFBP (insulin-like growth factor binding protein) 6 genes with the model group ratio under this experiment condition, illustrate: can be by raising the expression of this gene after buccal tablet is intervened, slow down or prevent and treat the Fibrotic process of hepatocyte, the control alcoholic fatty liver is had positive effect.

3.3.4 Srd5a1: steroid 5 alpha-reductases, α peptide 1, distribution endoplasmic reticulum, microsome, 3-C-5 α steroid 4 dehydrogenases participate in cell signalling, Sex determination, cell differentiation.Can be converted into another kind of androgen-dihydrotestosterone by the catalysis testosterone, therefore play a significant role in property differentiation and androgen physiology, this enzyme has Srd5a 1,2 two isomers.Mainly be expressed in skin and fatty tissue and liver, but the reduction reaction of unsaturation steroid on the 4th, 5 carbon atom of the catalysis overwhelming majority makes activated glucocorticoid (GC) be converted into the metabolite of non-activity.Research finds, the glucocorticoid effect not only with blood circulation in the GC Horizontal correlation, also have the GC concentration of physiologically active closely related with tissue local.The Srd5a1 activity that strengthens in the liver causes serum cortisol (COR) clearance rate to increase, and then compensatory hypothalamo-pituitary-adrenal axis (HPA) increased activity, COR secretes increase, further cause abdominal obesity and MS(MS to refer to a series of metabolism disorders and the gathering of cardiovascular and cerebrovascular vessel risk factor on same individuality, be the syndrome of the multiple Developmental and Metabolic Disorder clinical signs such as obesity, hypertension, dyslipidemia and impaired glucose tolerance).

This experiment condition drag group and natural matched group ratio, the up-regulated of Srd5a1 gene 2.6 times, illustrate: model group causes the serum cortisol clearance rate to increase by improving Srd5a1 gene expression enhancing Srd5a1 activity, so that MS appears in model group, finally facilitates fat to become.

Under this experiment condition with after the buccal tablet intervention with intervene before alcoholic fatty liver model group ratio, the down-regulated expression of Srd5a1 gene 2.72 times, illustrate: buccal tablet of the present invention can be by this gene expression of downward modulation, improve owing to the metabolism syndrome of indulging in excessive drinking and high fat diet brings, this has explained the reason why the bee pollen buccal tablet can prevent and treat metabolism syndrome from another point of view.

In a word, show the product of the present invention process of can the effective participation body relieving the effect of alcohol by above test, and effectively control because the fatty liver of excessive drinking and Induced by High Fat Diet.Product of the present invention can improve hepatocyte activity, improves the multiple biochemical indicator of blood, and prevention is because the fatty liver that long-term excessive drinking and high fat diet cause, the health care of safeguarding and improve the alcoholic fatty liver of Chinese is significant.

Claims (2)

1. the bee pollen water extract buccal tablet of control alcoholic fatty liver is characterized in that mainly being comprised of lyophilized powder, Sorbitol, starch slurry, magnesium stearate and the Mentholum alcoholic solution of the molecular weight of obtaining with the bee pollen water extracting method less than the bee pollen water extract of 5000D.

2. the bee pollen water extract buccal tablet of described control alcoholic fatty liver according to claim 1, it is characterized in that described lyophilized powder, Sorbitol, starch slurry, magnesium stearate, and the Mentholum alcoholic solution accounts for respectively 50～85%, 5～25%, 5～25%, 0.1～1.0%, 0.1～0.4% of buccal tablet gross mass.

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