CN105456520A - Pharmaceutical formula for treating alcoholic liver disease and experimental method - Google Patents

Pharmaceutical formula for treating alcoholic liver disease and experimental method Download PDF

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CN105456520A
CN105456520A CN201511008150.8A CN201511008150A CN105456520A CN 105456520 A CN105456520 A CN 105456520A CN 201511008150 A CN201511008150 A CN 201511008150A CN 105456520 A CN105456520 A CN 105456520A
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wine
proheparin
anion
alcoholic liver
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孙世萍
郭香云
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Yankuang Group Co Ltd General Hospital
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Abstract

The invention discloses a pharmaceutical formula for treating an alcoholic liver disease and an experimental method. Compared with the prior art, an animal experiment proves that the liver function index can be obviously lowered and morphological pathology changes of fatty change, fibrillation and the like are inhibited by a jiuganning (Chinese character) granule combined with an anion therapeutic apparatus in the aspect of improving MDA, SOD, GSH, immunohistochemistry and the like of an alcoholic liver injury; and the pharmaceutical formula has excellent functions of resisting oxidation, scavenging free radicals and stabilizing a cytomembrane, and has an accurate anti-hepatic injury effect. Powerful experimental basis and clinical foundation are provided for the directions of pathomechanism of the alcoholic liver disease and treatment of the alcoholic liver disease by the traditional Chinese medicine combined with anions by the research; and a new direction is provided for research on the pathomechanism of the alcoholic liver disease and green therapy of combination of the traditional Chinese medicine and the Western medicine in future.

Description

A kind of pharmaceutical formulation and experimental technique for the treatment of alcoholic liver disease
Technical field
The present invention relates to a kind of medical medicine, particularly relate to a kind of pharmaceutical formulation and experimental technique for the treatment of alcoholic liver disease.
Background technology
Alcoholic liver disease is the disease that long-term excessive beverage wine based article causes based on liver injury, and the initial stage is usually expressed as fatty liver, and then can develop into alcoholic hepatitis, alcoholic fibrosis and alcoholic cirrhosis; Even extensive hepatic necrosis liver failure can be brought out during serious excessive drinking.In 20th century, latter stage, sickness rate was apparently higher than states such as America and Europes, and in recent years along with the change of expanding economy and people life style, China's alcoholic liver disease has growing gesture.In the face of this present situation, under the guidance of Yin Xiaoxuan tutor, develop a series of scientific research for alcoholic liver injury therapeutic intervention in recent years, but still need improve further.
Summary of the invention
Object of the present invention is just to provide a kind of pharmaceutical formulation and experimental technique for the treatment of alcoholic liver disease to solve the problem.
The present invention is achieved through the following technical solutions above-mentioned purpose:
The present invention treats the pharmaceutical formulation of alcoholic liver disease, is made up of Radix Glycyrrhizae 6g, Herba Hyperici Japonici 15g, Radix Paeoniae Rubra 15g, Fructus Lycii 15g, Semen Cassiae 15g, Fructus Gardeniae 9g, Pericarpium Citri Reticulatae Viride 9g, Rhizoma Atractylodis Macrocephalae 15g, Radix Et Rhizoma Rhei 3g.
The present invention treats the drug study method of alcoholic liver disease, comprises the following steps:
(1) by Radix Glycyrrhizae 6g, Herba Hyperici Japonici 15g, Radix Paeoniae Rubra 15g, Fructus Lycii 15g, Semen Cassiae 15g, Fructus Gardeniae 9g, Pericarpium Citri Reticulatae Viride 9g, Rhizoma Atractylodis Macrocephalae 15g, the mixing of Radix Et Rhizoma Rhei 3g prescription herb in granule form, with boiled water punching in first 30 minutes to 100ml, administration volume: 10ml/kg, compound concentration: 0.918g/ml;
(2) wistar rat 125 is adopted, male, 250 ± 20g, rat adaptability raises 3d, then carry out Preliminary screening, weed out too active and too quiet rat, remaining rat is divided into 2 groups at random by body weight, blank group 12, model group 113,5 cage modelings;
(3) except normal group, model group all uses 56% Chinese liquor 1.0ml/100g gavage in morning every day for first week once, and second week starts will with dosage gavage every morning 1 time of 1.5mL/100g until 4th week;
(4) in 4th week end, each model group of arbitrary extracting 6 rats, are cooked the inspection of histopathology after being put to death by liver, determine whether modeling success;
(5) 107 rats remaining modeling reject 2, are divided into 7 groups, model group 15, wine proheparin group 20, anion high concentration group 15, anion low concentration group 15, and wine proheparin closes anion high concentration group 15; Wine proheparin closes anion low concentration group 15; Tiopronin group 15;
(6) gastric infusion 10ml/kg from the 5th week, blank group rat gives the water of equal volume, 12 weeks successive administration time, wine proheparin group, wine proheparin close anion high concentration group, wine proheparin closes the corresponding Chinese medicine decoction of anion low concentration group gavage, totally 12 weeks; Tiopronin group gavage tiopronin suspensoid, totally 12 weeks; Anion high concentration group, wine proheparin close anion high concentration group and use air vitamin rehabilitation machine MIS-05-03 space, and negative ion concentration is at 30--60 ten thousand/cm after testing 3; Anion low concentration group, wine proheparin close anion low concentration group and use air vitamin rehabilitation machine MIS-05-03 space, and negative ion concentration is at 5--20 ten thousand/cm after testing 3;
(7) after last administration, model group and the equal fasting of blank group can't help water 12 hours, then rat 10 is randomly drawed in every group, anaesthetize with 20% urethane after weighing respectively, in ventral aorta, blood is got at place, the centrifugal 10min of 3000rmp, leaves and takes the detection that serum need carry out related index, separation liver and spleen claim weight in wet base, calculate organ coefficient, the same position of hepatic tissue cut a fritter weigh after for doing tissue homogenate, measure index of correlation in liver.Remaining hepatic tissue needs to be divided into two parts, and a copy of it 10% formaldehyde is fixed, and needs to carry out inspection histopathology, and a neutral 10% formaldehyde fixedly carries out Immunohistochemical detection.
Beneficial effect of the present invention is:
The present invention is a kind of pharmaceutical formulation and experimental technique for the treatment of alcoholic liver disease, compared with prior art, the present invention passes through zoopery, improving the MDA of alcoholic liver injury, SOD, the aspect such as GSH and SABC all confirms wine Ganning granule associating anionic therapeutic apparatus, not only significantly reduces liver function index, suppresses the morphopathologies such as fat change, fibrosis to change; And there is effective antioxidation, scavenging free radicals, stabilizing cell membrane, there is clear and definite anti-liver injury effect.The direction of the pathomechanism that this research is alcoholic liver disease and Chinese medicine associating anion treatment alcoholic liver disease provides strong experimental basis and Clinical Basis, and the green treatment also for studying alcoholic liver disease pathomechanism and the combination of Chinese and Western medicine thereof from now on provides new direction.
Detailed description of the invention
The invention will be further described below:
The present invention treats the pharmaceutical formulation of alcoholic liver disease, is made up of Radix Glycyrrhizae 6g, Herba Hyperici Japonici 15g, Radix Paeoniae Rubra 15g, Fructus Lycii 15g, Semen Cassiae 15g, Fructus Gardeniae 9g, Pericarpium Citri Reticulatae Viride 9g, Rhizoma Atractylodis Macrocephalae 15g, Radix Et Rhizoma Rhei 3g.
The present invention treats the drug study method of alcoholic liver disease, comprises the following steps:
(1) by Radix Glycyrrhizae 6g, Herba Hyperici Japonici 15g, Radix Paeoniae Rubra 15g, Fructus Lycii 15g, Semen Cassiae 15g, Fructus Gardeniae 9g, Pericarpium Citri Reticulatae Viride 9g, Rhizoma Atractylodis Macrocephalae 15g, the mixing of Radix Et Rhizoma Rhei 3g prescription herb in granule form, with boiled water punching in first 30 minutes to 100ml, administration volume: 10ml/kg, compound concentration: 0.918g/ml;
(2) wistar rat 125 is adopted, male, 250 ± 20g, rat adaptability raises 3d, then carry out Preliminary screening, weed out too active and too quiet rat, remaining rat is divided into 2 groups at random by body weight, blank group 12, model group 113,5 cage modelings;
(3) except normal group, model group all uses 56% Chinese liquor 1.0ml/100g gavage in morning every day for first week once, and second week starts will with dosage gavage every morning 1 time of 1.5mL/100g until 4th week;
(4) in 4th week end, each model group of arbitrary extracting 6 rats, are cooked the inspection of histopathology after being put to death by liver, determine whether modeling success;
(5) 107 rats remaining modeling reject 2, are divided into 7 groups, model group 15, wine proheparin group 20, anion high concentration group 15, anion low concentration group 15, and wine proheparin closes anion high concentration group 15; Wine proheparin closes anion low concentration group 15; Tiopronin group 15;
(6) gastric infusion 10ml/kg from the 5th week, blank group rat gives the water of equal volume, 12 weeks successive administration time, wine proheparin group, wine proheparin close anion high concentration group, wine proheparin closes the corresponding Chinese medicine decoction of anion low concentration group gavage, totally 12 weeks; Tiopronin group gavage tiopronin suspensoid, totally 12 weeks; Anion high concentration group, wine proheparin close anion high concentration group and use air vitamin rehabilitation machine MIS-05-03 space, and negative ion concentration is at 30--60 ten thousand/cm after testing 3; Anion low concentration group, wine proheparin close anion low concentration group and use air vitamin rehabilitation machine MIS-05-03 space, and negative ion concentration is at 5--20 ten thousand/cm after testing 3;
(7) after last administration, model group and the equal fasting of blank group can't help water 12 hours, then rat 10 is randomly drawed in every group, anaesthetize with 20% urethane after weighing respectively, in ventral aorta, blood is got at place, the centrifugal 10min of 3000rmp, leaves and takes the detection that serum need carry out related index, separation liver and spleen claim weight in wet base, calculate organ coefficient, the same position of hepatic tissue cut a fritter weigh after for doing tissue homogenate, measure index of correlation in liver.Remaining hepatic tissue needs to be divided into two parts, and a copy of it 10% formaldehyde is fixed, and needs to carry out inspection histopathology, and a neutral 10% formaldehyde fixedly carries out Immunohistochemical detection.
Research process and result:
Within first 4 weeks, to rat modeling, in 4th week end, each model group of arbitrary extracting 6 rats, are cooked the inspection of histopathology after being put to death by liver, determine whether modeling success.Cause alcoholic liver injury model, take weekly rat body weight once, blank group 12 animals and model group 113 the weight of animals Homogeneity between groups before modeling, statistics compares without significant difference (P>0.05), first week after modeling, point its body weight of another name, in model group, rat body weight significantly reduces, contrast with blank group, there is notable difference (P<0.01).Observe to surrounding body weight visible, model group is organized poor apart from increasing with blank always, and prompting modeling causes obvious impact to rat general status.
Successive administration is after 3 months, take rat body weight, peel off each group of liver tissues of rats, according to formulae discovery organ index, between organizing, statistics compares, in model group, every index of liver is all obviously high than blank group, contrast with blank group and have very high significant difference (P<0.01), change between comparison model group, each administration group each index of reduction liver all in various degree, wherein the effect of wine proheparin conjunction anion high concentration group is given prominence to, and compares have significant difference (P<0.01) with model group.
Wine proheparin closes anion to the impact of Biochemical Indices In Serum, significantly reduces the concentration (p is all less than 0.01) of AST, ALT in serum, significantly can reduce serum TC, TG concentration.Measure MDA, SOD, GSH in serum, reagent thing group improves the above-mentioned change of rat model in various degree, reduces Serum Free Radical content, and wine proheparin coordinates the effect of anion group the strongest.
Wine proheparin closes anion to the impact of liver tissues of rats MDA, SOD, GSH, can significantly improve SOD level in its tissue (p < 0.01), and effect is it is preferred that wine proheparin coordinates anion group.
Liver histopathology aspect, wine proheparin closes anion high concentration group, wine proheparin closes anion low concentration group: figure has no obvious pathological change, but two groups all occur a routine liver stove inflammatory lesion, degraded, many places spotty necrosis inflammation.
SABC aspect, the surface density that in model group, CD14 positive expression goes out compares blank group does not have significant difference, and the difference of administration group is also just nonsensical.But positive rate has significant difference (p < 0.05), and compared with model group, the CD14 the positive expression rate that wine proheparin closes anion high concentration and low concentration group all has reduction, has significant significant difference (p < 0.01).
Comprehensive analysis, successive administration, after 12 weeks, finds that wine proheparin closes anion group and obviously reduces liver index, compares have significant difference (P<0.01) with model group.Improving model group rats Serum ALT, AST, TC, TG, HDL, LDL, FFA, GGT index level, wine proheparin coordinates anion two dosage groups to compare with other model group remarkable significant difference (p < 0.01, p < 0.05), other two groups all without obvious significant difference (P>0.05).Wine proheparin and anion group are significantly reducing in SOD level in Serum Free Radical content, raising tissue, reduction serum FFA level etc., and curative effect is better than other model group.
Comprehensive therapeutic effect is analyzed
Confirm wine Ganning granule associating anion treatment alcoholic liver disease determined curative effect by zoopery, particular content is as follows:
(1) antioxidation, scavenging free radicals, the liver protecting and ALT lowering
Successive administration, after 12 weeks, finds that wine proheparin closes anion group and reduces liver index, compares have significant difference (P<0.01) with model group.Improving model group rats Serum ALT, AST, TC, TG, HDL, LDL, FFA, GGT index level, wine proheparin coordinates anion two dosage groups to compare with other model group remarkable significant difference (P < 0.01, P < 0.05), other two groups all without obvious significant difference (P>0.05).Wine proheparin and anion group are significantly reducing in SOD level in Serum Free Radical content, raising tissue, reduction serum FFA level etc., and curative effect is better than other model group.
(2) reduce inflammation, repair wounded hepatocytes
To histopathologic examination, wine proheparin closes anion high concentration group, wine proheparin closes anion low concentration group: figure has no obvious pathological change, two groups all occur a routine liver stove inflammatory lesion, degraded, outside the spotty necrosis inflammation of many places.
(3) blood fat function improves
Wine proheparin can have stronger lipoid peroxidization resistant, and anion has stronger poised effect, and both share and can comparatively significantly improve patients serum's blood lipid level.
(4) hepatic fibrosis is improved
Wine proheparin can not only alleviate hepatic fibrosis, and anion also can strengthen antioxidative effect, and conbined usage more effectively can control or improve the hepatic fibrosis occurred.
(5) body physiological function is maintained
Wine Ganning granule, based on eliminating damp-heat, meets the main pathogenesis of patients with alcoholic liver disease, its contained drug modern pharmacological research all in various degree there is the liver protecting and ALT lowering, alleviate the effects such as cellular inflammation; Anion can effective buffered acid environment, and promote intracellular various metabolism, maintain body normal physiological function, therefore have defying age, enhancing immunity function, Papillary more can regulate immunity of organism, the liver protecting, repairs impaired hepatocyte.
More than show and describe ultimate principle of the present invention and principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description just illustrates principle of the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.

Claims (2)

1. treat a pharmaceutical formulation for alcoholic liver disease, it is characterized in that: be made up of Radix Glycyrrhizae 6g, Herba Hyperici Japonici 15g, Radix Paeoniae Rubra 15g, Fructus Lycii 15g, Semen Cassiae 15g, Fructus Gardeniae 9g, Pericarpium Citri Reticulatae Viride 9g, Rhizoma Atractylodis Macrocephalae 15g, Radix Et Rhizoma Rhei 3g.
2. treat a drug study method for alcoholic liver disease, it is characterized in that, comprise the following steps:
(1) by Radix Glycyrrhizae 6g, Herba Hyperici Japonici 15g, Radix Paeoniae Rubra 15g, Fructus Lycii 15g, Semen Cassiae 15g, Fructus Gardeniae 9g, Pericarpium Citri Reticulatae Viride 9g, Rhizoma Atractylodis Macrocephalae 15g, the mixing of Radix Et Rhizoma Rhei 3g prescription herb in granule form, with boiled water punching in first 30 minutes to 100ml, administration volume: 10ml/kg, compound concentration: 0.918g/ml;
(2) wistar rat 125 is adopted, male, 250 ± 20g, rat adaptability raises 3d, then carry out Preliminary screening, weed out too active and too quiet rat, remaining rat is divided into 2 groups at random by body weight, blank group 12, model group 113,5 cage modelings;
(3) except normal group, model group all uses 56% Chinese liquor 1.0ml/100g gavage in morning every day for first week once, and second week starts will with dosage gavage every morning 1 time of 1.5mL/100g until 4th week;
(4) in 4th week end, each model group of arbitrary extracting 6 rats, are cooked the inspection of histopathology after being put to death by liver, determine whether modeling success;
(5) 107 rats remaining modeling reject 2, are divided into 7 groups, model group 15, wine proheparin group 20, anion high concentration group 15, anion low concentration group 15, and wine proheparin closes anion high concentration group 15; Wine proheparin closes anion low concentration group 15; Tiopronin group 15;
(6) gastric infusion 10ml/kg from the 5th week, blank group rat gives the water of equal volume, 12 weeks successive administration time, wine proheparin group, wine proheparin close anion high concentration group, wine proheparin closes the corresponding Chinese medicine decoction of anion low concentration group gavage, totally 12 weeks; Tiopronin group gavage tiopronin suspensoid, totally 12 weeks; Anion high concentration group, wine proheparin close anion high concentration group and use air vitamin rehabilitation machine MIS-05-03 space, and negative ion concentration is at 30--60 ten thousand/cm after testing 3; Anion low concentration group, wine proheparin close anion low concentration group and use air vitamin rehabilitation machine MIS-05-03 space, and negative ion concentration is at 5--20 ten thousand/cm after testing 3;
(7) after last administration, model group and the equal fasting of blank group can't help water 12 hours, then rat 10 is randomly drawed in every group, anaesthetize with 20% urethane after weighing respectively, in ventral aorta, blood is got at place, the centrifugal 10min of 3000rmp, leaves and takes the detection that serum need carry out related index, separation liver and spleen claim weight in wet base, calculate organ coefficient, the same position of hepatic tissue cut a fritter weigh after for doing tissue homogenate, measure index of correlation in liver.Remaining hepatic tissue needs to be divided into two parts, and a copy of it 10% formaldehyde is fixed, and needs to carry out inspection histopathology, and a neutral 10% formaldehyde fixedly carries out Immunohistochemical detection.
CN201511008150.8A 2015-12-29 2015-12-29 Pharmaceutical formula for treating alcoholic liver disease and experimental method Pending CN105456520A (en)

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Application publication date: 20160406