CN102552332A - Application of Bacillus licheniformis live bacteria in preparation of medicine for preventing and treating intestinal endotoxemia - Google Patents

Application of Bacillus licheniformis live bacteria in preparation of medicine for preventing and treating intestinal endotoxemia Download PDF

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CN102552332A
CN102552332A CN2011103960911A CN201110396091A CN102552332A CN 102552332 A CN102552332 A CN 102552332A CN 2011103960911 A CN2011103960911 A CN 2011103960911A CN 201110396091 A CN201110396091 A CN 201110396091A CN 102552332 A CN102552332 A CN 102552332A
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bacillus licheniformis
medicine
intestinal endotoxemia
viable bacteria
acute
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苏显英
顾佩菲
刘立新
马大中
陈铮
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Northeast Pharmaceutical Group Shenyang No1 Pharmaceutical Co Ltd
NORTHEAST PHARMACEUTICAL (SHENYANG) TECHNOLOGY DEVELOPMENT Co Ltd
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Northeast Pharmaceutical Group Shenyang No1 Pharmaceutical Co Ltd
NORTHEAST PHARMACEUTICAL (SHENYANG) TECHNOLOGY DEVELOPMENT Co Ltd
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Abstract

The invention relates to an application of Bacillus licheniformis live bacteria which is applied in the field of biotechnology in preparation of medicine for preventing acute and chronic intestinal endotoxemia and medicine for treating chronic intestinal endotoxemia; an application of the Bacillus licheniformis live bacteria in preparation of medicine for preventing acute and chronic intestinal endoxemia; and an application of the Bacillus licheniformis live bacteria in preparation of medicine for treating chronic intestinal endotoxemia. The intestinal endotoxemia is caused by factor causing damage to liver; a dosage of the Bacillus licheniformis live bacteria is 0.45-1.35 billion live bacteria per kilogram every day. The Bacillus licheniformis live bacteria provided by the invention ameliorates the intestinal endotoxemia caused by acute and chronic liver injury in rat induced by thioacetamide, improves histopathology change of the liver injury of rat, relieves lipid peroxidatic injury of hepatic tissue when chronic liver injury occurs, and partially decreases levels of serum glutamic pyruvic transaminase, glutamic-oxalacetic transaminease and lactic dehydrogenase.

Description

The bacillus licheniformis viable bacteria is used for preventing and treating the application of toxicity mass formed by blood stasis medicine in the property of intestinal source as preparation
Technical field
The present invention relates to the new purposes of a kind of Bacillus licheniformis viable bacteria in the biological technical field, the application that is used for preventing the acute and chronic intestinal endotoxemia and treats chronic intestinal endotoxemia medicine as preparation.
Background technology
Berg in 1979 propose the notion of " antibacterial displacement " first, it are defined as " antibacterial that lives in the intestinal is invaded the position beyond the intestinal through intestinal mucosa, like mesenteric lymph node, liver, spleen, blood so that the course of infection of whole body ".Nineteen ninety Alexander is " microorganism displacement " with its expansion of content, and promptly " live or dead antibacterial and product thereof comprises endotoxin in the intestinal, invades the intestinal process at position in addition through the complete intestinal mucosal barrier of anatomy.Nineteen ninety-five is taught in domestic propose first " intestinal endotoxemia theory " by the Han Dewu of Mountain Western Medicine S University, thinks toxicity mass formed by blood stasis decisive role in the incidence and development of hepatopathy in the property of intestinal source, and this theory progressively obtains approval both at home and abroad.Think the various factors that cause hepar damnification at present; Like hepatitis virus, ethanol, medicine and poisonous substance etc.; Except that the cause of disease and pathogenesis through separately cause " constitutional hepatic injury ", intestinal endotoxemia (cause level of endotoxin increases substantially in the blood of human body) appears in body mostly in the hepatopathy incidence and development.The endotoxin that appearance can detect in the circulation blood is referred to as endotoxemia, wherein without gram negative bacteria (gram-negative bacteria, G-antibacterial) the infected, is called intestinal endotoxemia.Intestinal endotoxemia causes the effect of hepar damnification to have substantially: (1) makes the cellular immune function of sickened body low, and viral hepatitis is unfavorable for killing and removing of virus; (2) endotoxin can activate Kupffer Cell and discharges a large amount of cytokines, and its cytotoxicity of performances such as inflammatory mediator directly damages hepatocyte; (3) endotoxin makes liver generation microcirculation disturbance, makes hepatic tissue generation hypoxic-ischemic and causes hepatocellular degeneration and necrosis.This shows that intestinal endotoxemia can " Secondary cases hepatic injury " take place owing to above-mentioned effect make liver, its to the development of hepatopathy with lapse to important role and influence.Intestinal endotoxemia serious symptom person often causes over-drastic inflammatory reaction, and it is downright bad that severe hepatic takes place, and cause hepatitis gravis, even acute hepatic failure takes place.Therefore at prevention and treatment treatment constitutional; Should note the treatment of intestinal endotoxemia in the time of the Secondary cases hepatic injury; And often there are the relatively poor and immunologic tolerance of immunologic function in viral hepatitis or hepatopath, so virus can not get removing the disease obstinate.
Use antiviral drugs to treat for intestinal endotoxemia clinically at present more, like interferon, lamivudine etc., but all do not see obvious curative effects.The acidificable intestinal of oral lactulose, interfere with bacterial breeding reduces the plasma endotoxin level to a certain extent, residues in intravital endotoxin biological effect but can't block, and can't improve the Liver Microcirculation by the intestinal endotoxemia mediation.Therefore inquire into the new Therapeutic Method of intestinal endotoxemia and medication preparation has very big clinical value.
Normal gut barrier is made up of these four kinds of Fundamentals of intestinal biological barrier, mechanical barrier, immune defence and intestinal liver axle, is the key mechanism of displacements such as body defence intestinal bacteria and endotoxin.Normal intestinal microbes is kept stable equilibrium each other through bacterial antagonism, like contact inhibition, antimicrobial agent and competition connecting portion and nutrition.The displacement of antibacterial and endotoxin can take place when normal bowel barrier function obstacle.Severe trauma, burn, critical patient, multiple organ failure, MOF patient, life-threatening bacteremia, enterobacterial infection patient the antibacterial displacement often occurs, but do not have clear and definite focus of infection.The antibacterial amount of migrating is relevant with the damage weight.But the promotion intestinal endotoxin of circulation endotoxin positive feedback displacement.In case the intestinal barrier is depleted, liver is removed intestinal source property antibacterial and endotoxic ability just becomes the determiner whether whole body sepsis and organ injury at a distance take place.The antibacterial and the endotoxin of displacement directly damage liver or increase the weight of existing damage, and endotoxin is able to finally get into systemic circulation.Intravital endotoxin activates Kupffer cell and other phagocyte; Discharge cytokine and other inflammatory mediator; Cause organ injury at a distance; For the generation of multiple organ dysfunction syndrome and intestinal source property septicemia state, intestinal endotoxin displacement has more clinical meaning than the antibacterial displacement, and the normal barrier that therefore how to recover intestinal for the treatment of intestinal endotoxemia just seems particularly important.
Microbial ecological agent is meant under the microecology guide of theory, adjustment ecological disturbance, the biological product that keep microecological balance, the physiologically active goods that improve host's (people, the animals and plants) health level or the state that improves health and metabolite thereof and promote physiology flora growth and breeding.Microbial ecological agent-bacillus licheniformis viable bacteria can be improved intestinal environment, reduces endotoxic absorption, in the treatment of posthepatitic cirrhosis, has potential clinical value.Bacillus licheniformis viable bacteria, its mechanism are that it can cause suboxides reduction potential (Eh) on the one hand and at a large amount of oxygen of local environment consumption, with the growth of ancestral home bacterium such as promotion bacillus bifidus, thereby reach the purpose of adjusting alteration of intestinal flora; Promptly adjust the intestinal microecology environment through environment change on the other hand and reach the equilibrated purpose of adjustment intestinal microecology.The alteration of intestinal flora disease that be mainly used in clinically that treatment adult is acute, chronic diarrhea and a variety of causes causes, infantile diarrhea, prevention infectious intestinal disease etc.Existing clinical research shows, cirrhotic ascites companion spontaneous peritonitis patient, oral bacillus licheniformis viable capsule, each 4; Every day 3 times, 10 days was 1 course of treatment, observed the situation of change of two groups of clinical symptoms, sign, ascites routine and cultivation and liver functions after 2 courses of treatment; Use the antibiotic matched group relatively with 39 examples are simple, the bacillus licheniformis viable bacteria can recover normal intestinal flora, improves liver function; Enhance immunity reduces endotoxemia, has sure therapeutical effect.
Up to now, the insight clothing bacillus cereus preparation report that is used to prevent the acute and chronic intestinal endotoxemia and treats the correlational study of chronic intestinal endotoxemia medicine not also.Therefore, research Bacillus licheniformis preparation is used to prevent the acute and chronic intestinal endotoxemia and treats chronic intestinal endotoxemia significant.
Summary of the invention
The purpose of this invention is to provide the application that a kind of bacillus licheniformis viable bacteria is used for preventing the acute and chronic intestinal endotoxemia and treats chronic intestinal endotoxemia medicine as preparation; The Bacillus licheniformis viable bacteria reduces the intestinal endotoxemia that causes when thioacetamide causes the rat acute and chronic liver injury; The histopathology that improves its hepatic injury changes; The lipid peroxidation injury of hepatic tissue when alleviating chronic hepatic injury, part reduces serum glutamic pyruvic transminase, glutamic oxaloacetic transaminase, GOT and lactic dehydrogenase enzyme level.
The objective of the invention is to realize like this: the application that a kind of bacillus licheniformis viable bacteria is used for preventing the acute and chronic intestinal endotoxemia and treats chronic intestinal endotoxemia medicine as preparation; The bacillus licheniformis viable bacteria is used for preventing the application of acute and chronic intestinal endotoxemia medicine as preparation, and the bacillus licheniformis viable bacteria is used for treating the application of chronic intestinal endotoxemia medicine as preparation; Said acute and chronic intestinal endotoxemia can be caused by the various hepar damnification factors that cause, and comprises hepatitis virus, ethanol, medicine, poisonous substance, liver cirrhosis, hepatocarcinoma and other any factors that causes hepar damnification; In the said disease of treatment claim 2, have the reparation hepatic injury, improve the curative effect of liver function; When the generation of diseases such as obstructive jaundice, pancreatitis, various shocks and when following intestinal endotoxemia, the preparation of bacillus licheniformis viable bacteria for above-mentioned several kinds of diseases with intestinal endotoxemia the positive therapeutic effect is also arranged; Recommend using dosage said bacillus licheniformis viable bacteria adult's every day is 0.45-1.35 hundred million viable bacterias/kg.
Main points of the present invention are that the bacillus licheniformis viable bacteria is used for preventing the application of acute and chronic intestinal endotoxemia medicine as preparation, and the bacillus licheniformis viable bacteria is used for treating the application of chronic intestinal endotoxemia medicine as preparation.The present invention inquires into the pharmacotoxicological effect of bacillus licheniformis viable bacteria through zoopery, is clinical a kind of new pharmaceutical usage and the method for using of providing.Its principle is that this medicine is development on hepatopathy incidence and development " intestinal endotoxemia " basis, and this medicine also has the intestinal of alleviating source property level of endotoxin, resists hepar damnification simultaneously, improves the effect of liver function; Simultaneously because intestinal endotoxemia lapses to important influence for the incidence and development and the prognosis of diseases such as obstructive jaundice, pancreatitis, various shocks, therefore the patient for above-mentioned disease is suitable for simultaneously.It is extensive that this medicine is suitable for the crowd, is applicable to that all can cause the factor of hepar damnification, and like hepatitis virus, ethanol, medicine and poisonous substance, the prevention and the treatment of the endotoxemia that causes etc. reason do not have limited hepatopath.The present invention is directed to the specific treatment medicine that does not still have at present the intestinal endotoxemia that hepatic disease causes clinically; Clear and definite bacillus licheniformis viable bacteria can be used as effective ingredient; With the zoopery curative effect is foundation; Providing a kind of treats interior toxicity mass formed by blood stasis and improves liver function, the new use of opposing hepatic injury.
The application that a kind of bacillus licheniformis viable bacteria is used for preventing the acute and chronic intestinal endotoxemia and treat chronic intestinal endotoxemia medicine as preparation compared with prior art; Have the Bacillus licheniformis viable bacteria and reduce the intestinal endotoxemia that causes when thioacetamide causes the rat acute and chronic liver injury; The histopathology that improves its hepatic injury changes; The lipid peroxidation injury of hepatic tissue when alleviating chronic hepatic injury; Part reduces advantages such as serum glutamic pyruvic transminase, glutamic oxaloacetic transaminase, GOT and lactic dehydrogenase enzyme level, will be widely used in the biological technical field.
Description of drawings:
Below in conjunction with accompanying drawing and embodiment the present invention is elaborated.
Fig. 1 is acute liver damage prevention rats in normal control group hepatic tissue HE dyeing * 100.
Fig. 2 is acute liver damage prevention TAA model group liver tissues of rats HE dyeing * 100.
Fig. 3 is acute liver damage prevention bacillus licheniformis viable bacteria low dose group liver tissues of rats HE dyeing * 100.
Fig. 4 is acute liver damage prevention bacillus licheniformis viable bacteria high dose group liver tissues of rats HE dyeing * 100.
Fig. 5 is acute liver damage prevention rats in normal control group hepatic tissue HE dyeing * 400.
Fig. 6 is acute liver damage prevention TAA model group liver tissues of rats HE dyeing * 400.
Fig. 7 is acute liver damage prevention bacillus licheniformis viable bacteria low dose group liver tissues of rats HE dyeing * 400.
Fig. 8 is acute liver damage prevention bacillus licheniformis viable bacteria high dose group liver tissues of rats HE dyeing * 400.
Fig. 9 is chronic hepatic injury prevention rats in normal control group hepatic tissue HE dyeing * 100.
Figure 10 is chronic hepatic injury prevention TAA model group liver tissues of rats HE dyeing * 100.
Figure 11 is chronic hepatic injury prevention bacillus licheniformis viable bacteria low dose group liver tissues of rats HE dyeing * 100.
Figure 12 is chronic hepatic injury prevention bacillus licheniformis viable bacteria high dose group liver tissues of rats HE dyeing * 100.
Figure 13 is chronic hepatic injury prevention rats in normal control group hepatic tissue HE dyeing * 400.
Figure 14 is chronic hepatic injury prevention TAA model group liver tissues of rats HE dyeing * 400.
Figure 15 is chronic hepatic injury prevention bacillus licheniformis viable bacteria low dose group liver tissues of rats HE dyeing * 400.
Figure 16 is chronic hepatic injury prevention bacillus licheniformis viable bacteria high dose group liver tissues of rats HE dyeing * 400.
Figure 17 is chronic hepatic injury medicine for treatment rats in normal control group hepatic tissue HE dyeing * 100.
Figure 18 is chronic hepatic injury medicine for treatment TAA model group liver tissues of rats HE dyeing * 100.
Figure 19 is chronic hepatic injury medicine for treatment bacillus licheniformis viable bacteria low dose group liver tissues of rats HE dyeing * 100.
Figure 20 is chronic hepatic injury medicine for treatment bacillus licheniformis viable bacteria high dose group liver tissues of rats HE dyeing * 100.
Figure 21 is chronic hepatic injury medicine for treatment rats in normal control group hepatic tissue HE dyeing * 400.
Figure 22 is chronic hepatic injury medicine for treatment TAA model group liver tissues of rats HE dyeing * 400.
Figure 23 is chronic hepatic injury medicine for treatment bacillus licheniformis viable bacteria low dose group liver tissues of rats HE dyeing * 400.
Figure 24 is chronic hepatic injury medicine for treatment bacillus licheniformis viable bacteria high dose group liver tissues of rats HE dyeing * 400.
The specific embodiment
Medicine zoopery scheme of the present invention is following.The animal object of observation is acute due to the thioacetamide (TAA); Intestinal endotoxemia due to the chronic hepatic injury rat; The variation of detection plasma endotoxin, serum glutamic pyruvic transminase (ALT), serum glutamic oxalacetic transaminase (AST), serum malonaldehyde (MDA), serum lactate dehydrogenase (SLD) (LDH) is also carried out the hepatic pathology credit and is analysed, and to observe the lichens bacillus living intestinal endotoxemia is had prevention and therapeutical effect.
160 of cleaning level SD rats, male, body weight 240-290g is divided into 3 at random and organizes greatly: 40 of acute liver damage prevention group, 60 of chronic hepatic injury prevention group, 60 of chronic hepatic injury medicine for treatment groups.Each big group is divided into 4 groups again at random: normal control group, TAA model group, bacillus licheniformis viable bacteria low dose group, bacillus licheniformis viable bacteria high dose group.Concrete experimental program is following.
1. acute liver damage prevention group
40 of cleaning level SD rats, male, body weight 240-290g is divided into 4 groups at random.
1. normal control group:
Free diet was fed 9 days.
2. TAA model group:
Free diet was fed 7 days, the 8th day beginning subcutaneous injection TAA, 250mg/kg, 1 time/day, continuous 2 days.
3. bacillus licheniformis viable bacteria low dose group:
The Bacillus licheniformis viable bacteria is irritated stomach, 5mg/kg, 1 time/day, continuous 9 days; The 8th day subcutaneous injection TAA when irritating stomach, the TAA usage is with the TAA model group, continuous 2 days.
4. bacillus licheniformis viable bacteria high dose group:
The Bacillus licheniformis viable bacteria is irritated stomach, 15mg/kg, 1 time/day, continuous 9 days; The 8th day subcutaneous injection TAA when irritating stomach, the TAA usage is with the TAA model group, continuous 2 days.
The acute liver damage prevention group is divided into groups signal as follows:
The 1st day The 2nd day The 3rd day The 4th day The 5th day The 6th day The 7th day The 8th day The 9th day
1. normal control group
Free diet was fed 9 days
[0052]2. TAA model group
Figure BDA0000115325070000071
3. bacillus licheniformis viable bacteria low dose group
Figure BDA0000115325070000072
2.1 chronic hepatic injury prevention group
60 of cleaning level SD rats, male, body weight 240-290g is divided into 4 groups at random.
1. normal control group:
Free diet fed for 7 weeks.
2. TAA model group:
Subcutaneous injection TAA, 100mg/kg, 3 times/week, continuous 7 weeks.
3. bacillus licheniformis viable bacteria low dose group:
The TAA usage is with the TAA model group, continuous 7 weeks; In subcutaneous injection TAA, give the Bacillus licheniformis viable bacteria and irritate stomach, 5mg/kg, 1 time/day, continuous 7 weeks.
4. bacillus licheniformis viable bacteria high dose group:
The TAA usage is with the TAA model group, continuous 7 weeks; In subcutaneous injection TAA, give the Bacillus licheniformis viable bacteria and irritate stomach, 15mg/kg, 1 time/day, continuous 7 weeks.
The chronic hepatic injury prevention group is divided into groups signal as follows:
The 1st week The 2nd week The 3rd week The 4th week The 5th week The 6th week The 7th week
1. normal control group
Free diet fed for 7 weeks
2. TAA model group
Subcutaneous injection TAA, 100mg/kg, 3 times/week, continuous 7 weeks
3. bacillus licheniformis viable bacteria low dose group
Figure BDA0000115325070000081
4. bacillus licheniformis viable bacteria high dose group
Figure BDA0000115325070000082
2.2 chronic hepatic injury medicine for treatment group
60 of cleaning level SD rats, male, body weight 240-290g is divided into 4 groups at random.
1. normal control group:
Free diet fed for 9 weeks.
2. TAA model group:
Subcutaneous injection TAA, 100mg/kg, 3 times/week, continuous 9 weeks.
3. bacillus licheniformis viable bacteria low dose group:
The TAA usage is with the TAA model group, continuous 9 weeks; Subcutaneous injection TAA begins to give the Bacillus licheniformis viable bacteria and irritates stomach, 5mg/kg, 1 time/day, continuous 7 weeks after 2 weeks.
4. bacillus licheniformis viable bacteria high dose group:
The TAA usage is with the TAA model group, continuous 9 weeks; Subcutaneous injection TAA begins to give the Bacillus licheniformis viable bacteria and irritates stomach, 15mg/kg, 1 time/day, continuous 7 weeks after 2 weeks.
Chronic hepatic injury medicine for treatment component group is illustrated as follows:
The 1st week The 2nd week The 3rd week The 4th week The 5th week The 6th week The 7th week The 8th week The 9th week
1. normal control group
Free diet fed for 9 weeks
2. TAA model group
Subcutaneous injection TAA, 100mg/kg, 3 times/week, continuous 9 weeks
3. bacillus licheniformis viable bacteria low dose group
Figure BDA0000115325070000091
4. bacillus licheniformis viable bacteria high dose group
Figure BDA0000115325070000092
Experimental effect of the present invention is following: 1. the Bacillus licheniformis viable bacteria can reduce the intestinal endotoxemia (table 1,2,3) that causes when thioacetamide (TAA) causes the rat acute and chronic liver injury; The histopathology that 2. can improve its hepatic injury changes (table 4,5,6); 3. the lipid peroxidation injury of hepatic tissue improves liver function in the time of can alleviating chronic hepatic injury, and part reduces serum glutamic pyruvic transminase (ALT) (table 7; 8,9), glutamic oxaloacetic transaminase, GOT (AST) (table 10,11; 12), malonaldehyde (MDA) (table 13,14,15) and lactic acid dehydrogenase (LDH) (table 16; 17,18) level.The intestinal endotoxemia that causes when therefore, the Bacillus licheniformis viable bacteria causes the rat acute and chronic liver injury to TAA has prevention and therapeutical effect.
Rat plasma level of endotoxin
Figure BDA0000115325070000093
is respectively organized in the prevention of table 1 acute liver damage
Figure BDA0000115325070000094
Figure BDA0000115325070000101
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group;
Rat plasma level of endotoxin
Figure BDA0000115325070000102
is respectively organized in the prophylactic of table 2 chronic hepatic injury
Figure BDA0000115325070000103
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Rat plasma level of endotoxin is respectively organized in the medicine for treatment of table 3 chronic hepatic injury
Figure BDA0000115325070000105
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Table 1,2,3 explanations, acute liver damage TAA model group, chronic hepatic injury AA model group is compared with the normal control group, level of endotoxin significantly raise (P<0.05); After the bacillus licheniformis viable bacteria prevention administration, 5mg/kg, 15mg/kg can significantly reduce the level of endotoxin rising (P<0.05) that the acute and chronic liver injury rat model causes, and along with dosage increase effect is more obvious; Therapeutic gives bacillus licheniformis viable bacteria 5mg/kg; 15mg/kg also has remarkable result for the level of endotoxin of chronic hepatic injury rat model; Explain that the bacillus licheniformis viable bacteria has tangible preventive effect for the level of endotoxin rising that acute intestinal endotoxemia causes, the level of endotoxin that causes for chronic intestinal endotoxemia simultaneously raises tangible prevention and treatment is arranged.
The prevention of table 4 acute liver damage is respectively organized liver tissues of rats HE colored graph as analysis result
Figure BDA0000115325070000106
Figure BDA0000115325070000107
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
The prophylactic of table 5 chronic hepatic injury is respectively organized liver tissues of rats HE colored graph as analysis result
Figure BDA0000115325070000111
Figure BDA0000115325070000112
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
The medicine for treatment of table 6 chronic hepatic injury is respectively organized liver tissues of rats HE colored graph as analysis result
Figure BDA0000115325070000114
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Table 4; 5; 6 explanations; Acute and chronic TAA model is hindered the increase that all can cause the rat liver damaged area, gives the damaged area (P<0.05) that bacillus licheniformis viable bacteria 15mg/kg can reduce rat and the 5mg/kg group can reduce the damaged area of rat for Rats with Acute Liver Injury is preventative, but compares there was no significant difference with model group; Prevention is with after therapeutic gives the bacillus licheniformis viable bacteria, and the damaged area of chronic hepatic injury rat all has obviously and reduces, and along with dosage increases effect more obviously (P<0.05), explains that the bacillus licheniformis viable bacteria has tangible hepar damnification repair.
Rat blood serum glutamate pyruvate transaminase (ALT) level
Figure BDA0000115325070000115
is respectively organized in the prevention of table 7 acute liver damage
Figure BDA0000115325070000116
Rat blood serum glutamate pyruvate transaminase (ALT) level
Figure BDA0000115325070000117
is respectively organized in the prophylactic of table 8 chronic hepatic injury
Figure BDA0000115325070000118
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Rat blood serum glutamate pyruvate transaminase (ALT) level is respectively organized in the medicine for treatment of table 9 chronic hepatic injury
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group;
Table 7,8,9 explanations, acute liver damage TAA model group, chronic hepatic injury AA model group is compared with the normal control group, and the ALT level is significantly rising (P<0.05) all; After the bacillus licheniformis viable bacteria prevention administration, 5mg/kg, 15mg/kg can significantly reduce the ALT level rising (P<0.05) that the chronic hepatic injury rat causes; And it is not obvious after acute liver damage prevention administration group and the chronic hepatic injury treatment administration for the improvement effect of ALT.
Rat blood serum glutamic oxaloacetic transaminase, GOT (AST) level
Figure BDA0000115325070000124
is respectively organized in the prevention of table 10 acute liver damage
Figure BDA0000115325070000125
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Rat blood serum glutamic oxaloacetic transaminase, GOT (AST) level is respectively organized in the prophylactic of table 11 chronic hepatic injury
Figure BDA0000115325070000127
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group;
Rat blood serum glutamic oxaloacetic transaminase, GOT (AST) level
Figure BDA0000115325070000128
is respectively organized in the medicine for treatment of table 12 chronic hepatic injury
Figure BDA0000115325070000129
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Table 10,11,12 explanations; Acute and chronic TAA model is hindered the raising that all can cause rat blood serum glutamic oxaloacetic transaminase, GOT (AST) level; After prevention gave the bacillus licheniformis viable bacteria with therapeutic, chronic hepatic injury rat AST level all had obvious reduction (P<0.05), and prompting rats'liver function makes moderate progress; For Rats with Acute Liver Injury is preventative give the bacillus licheniformis viable bacteria after the AST level decrease, but compare there was no significant difference with model group.
Rat blood serum malonaldehyde (MDA) level
Figure BDA0000115325070000132
is respectively organized in the prevention of table 13 acute liver damage
Figure BDA0000115325070000133
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Rat blood serum malonaldehyde (MDA) level
Figure BDA0000115325070000134
is respectively organized in the prophylactic of table 14 chronic hepatic injury
Figure BDA0000115325070000135
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Rat blood serum malonaldehyde (MDA) level
Figure BDA0000115325070000136
is respectively organized in the medicine for treatment of table 15 chronic hepatic injury
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Table 13,14,15 explanations; Acute and chronic TAA model is hindered the raising that all can cause rat malonaldehyde (MDA) level; After prevention gave the bacillus licheniformis viable bacteria with therapeutic, chronic hepatic injury rat AST level all had obvious reduction (P<0.05), and prompting rats'liver function makes moderate progress; For Rats with Acute Liver Injury is preventative give the bacillus licheniformis viable bacteria after the MDA level decrease, but compare there was no significant difference with model group.
Rat blood serum lactic acid dehydrogenase (LDH) level is respectively organized in the prevention of table 16 acute liver damage
Figure BDA0000115325070000142
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Rat blood serum lactic acid dehydrogenase (LDH) level is respectively organized in the prophylactic of table 17 chronic hepatic injury
Figure BDA0000115325070000144
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Rat blood serum lactic acid dehydrogenase (LDH) level
Figure BDA0000115325070000145
is respectively organized in the medicine for treatment of table 18 chronic hepatic injury
Figure BDA0000115325070000146
Annotate: * compares P<0.05 with the normal control group; △ compares P<0.05 with the TAA model group
Table 16,17,18 explanations; Acute and chronic TAA model is hindered the raising that all can cause rat lactic acid dehydrogenase (LDH) level; After prevention gave the bacillus licheniformis viable bacteria with therapeutic, chronic hepatic injury rat LDH level all had obvious reduction (P<0.05), and prompting rats'liver function makes moderate progress; For Rats with Acute Liver Injury is preventative give the bacillus licheniformis viable bacteria after the LDH level decrease, but compare there was no significant difference with model group.
Conclusion:
The present invention mainly keeps the normal barrier function of intestinal through improving the intestinal microecology balance; Repair hepatic injury simultaneously; Improve liver function, on the incidence and development of the intestinal endotoxemia that causes of research hepatopathy and mechanism of action, new medicine and method is provided; Simultaneously because intestinal endotoxemia lapses to important influence for the incidence and development and the prognosis of diseases such as obstructive jaundice, pancreatitis, various shocks, thus this medicine for above-mentioned several kinds of diseases with intestinal endotoxemia the positive therapeutic effect is also arranged.

Claims (5)

1. application that the bacillus licheniformis viable bacteria is used for preventing the acute and chronic intestinal endotoxemia and treats chronic intestinal endotoxemia medicine as preparation; It is characterized in that: the bacillus licheniformis viable bacteria is used for preventing the application of acute and chronic intestinal endotoxemia medicine as preparation, and the bacillus licheniformis viable bacteria is used for treating the application of chronic intestinal endotoxemia medicine as preparation.
2. the application that a kind of bacillus licheniformis viable bacteria according to claim 1 is used for preventing the acute and chronic intestinal endotoxemia and treats chronic intestinal endotoxemia medicine as preparation; It is characterized in that: said acute and chronic intestinal endotoxemia can be caused by the various hepar damnification factors that cause, and comprises hepatitis virus, ethanol, medicine, poisonous substance, liver cirrhosis, hepatocarcinoma and other any factors that causes hepar damnification.
3. the application that a kind of bacillus licheniformis viable bacteria according to claim 1 is used for preventing the acute and chronic intestinal endotoxemia and treats chronic intestinal endotoxemia medicine as preparation; It is characterized in that: in the said disease of treatment claim 2; Have the reparation hepatic injury, improve the curative effect of liver function.
4. the application that a kind of bacillus licheniformis viable bacteria according to claim 1 is used for preventing the acute and chronic intestinal endotoxemia and treats chronic intestinal endotoxemia medicine as preparation; It is characterized in that: when the generation of diseases such as obstructive jaundice, pancreatitis, various shocks and when following intestinal endotoxemia, the preparation of bacillus licheniformis viable bacteria for above-mentioned several kinds of diseases with intestinal endotoxemia the positive therapeutic effect is also arranged.
According to claim 1 and 2 described a kind of bacillus licheniformis viable bacterias as the application that preparation is used for preventing the acute and chronic intestinal endotoxemia and treats chronic intestinal endotoxemia medicine, it is characterized in that: recommend using dosage said bacillus licheniformis viable bacteria adult's every day is 0.45-1.35 hundred million viable bacterias/kg.
CN2011103960911A 2011-12-02 2011-12-02 Application of Bacillus licheniformis live bacteria in preparation of medicine for preventing and treating intestinal endotoxemia Pending CN102552332A (en)

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Application publication date: 20120711