| Objective:The aim of the study is to establish alcoholic fatty liver disease modle rats.to explore the pathogenesis of alcoholic liver disease in pharmacology.and to discuss the treatment function and mechanism of butulin on alcoholic liver disease.Methods:72 SPF SD male rats, body weight 180-220g. after feeded adaptability 3d and were randomly divided into six groups(normal control group, model group, positive control group, betulin low-dose group, betulin middle-dose group, betulin high-dose group). and each group has twelve. The normal control group were fed with distilled water(9ml/kg/d) by filling the stomach, last 8 weeks:56% white spirit was respectively diluted with distilled water into alcohol concentration of 40% and 50%. and other five group were fed 40% white spirits(9ml/kg/d) by filling the stomach for two weeks, then the five groups were fed 50% white spirit(1 Oml/kg/d) for ten weeks. Normal control group and model group were respectively executed two rats at the fourth and eighth weekend, materials were taken and corresponding indicators were detected. After the alcoholic fatty liver disease model were successfully established. From the ninth week. The normal control group were still fed with distilled water(9ml/kg/d) by filling the stomach:The model group were fed with olive oil(9ml/kg/d) after fed with white spirit 1～2h; Yiganlin were gringed and dissolved in distilled water, and the positive control group were fed with Yiganling(100mg/kg/d) by filling the stomach after fed white spirit 1～2h. Betulin were dissolved in olive oil, the dose were that:low-dose (10mg/kg). middle-dose (20mg/kg), high-dose(40mg/kg). then betulin low-dose group.betulin middle-dose group and betulin high-dose group were respectively fed with corresponding dose betulin by filling the stomach after fed with white spirit 1～2h.Rats in each group were executed and materials were taken and corresponding indicators were detected at the twelveth weekend.Results: 1. Effect of betulin on the aocoholic fatty liver disease rats general conditionRats in normal control group were alive,fur is smooth,appetite,urine and stool were normal. Rats in Model group compared with other groups, the rats had poorer mental state,fur was lack luster, activities were less,food-intake and urine volume were less.stool were relatively rare soft.The mental status of rats in betulin each dose group were gradually improved,and the fur were gradually smoothed,activities. food-intake and urine volume were gradually increased, stool were becoming normal.2.Effect of betulin on the alcoholic fatty liver disease rats body weight and organ indexThe weight growth of model group were significant lower than normal control group at the twelveth weekend(P<0.05). The weight growth of betulin high-dose group were significant higher than normal control group at the twelveth weekend (P <0.05). The weight growth of each drug group were significant higher than model group at the twelveth weekend (P<0.05). Betulin high-dose group compare with positive control group, the weight growth at the twelveth weekend have no significant difference(P>0.05). The model group and each drug group compare with normal control group.the cardiac index,spleen index,lung index,kidney index,testis index of rats have no significant difference(P>0.05). The liver index of model group were significant higher than normal control group(P<0.05). The liver index of each drug group compare wirh normal control group have no significant difference(P>0.05). The liver index of betulin low-dose group were significant lower than model group(P <0.05). The liver index of betulin each dose group compare with positive control group have no significant difference(P>0.05).3.Effect of betulin on the alcoholic fatty liver disease rats liver tissue pathologyThe liver tissue of rats were observerd in the microscope.complete hepatic lobules were observerd in the normal control group rats.and the hepatic cells arranged as the radiate in central vein.hepatic cells cable structure were clear. But in the model group, the hepatic lobules were not complete.hepatic cells cable structure were disorder.liver sinus were disapper,the liver cells were swelling and degeneration.lipid droplets were seen in some cytoplasm.ballooning degeneration phenomenon were observerd in few cells.In the betulin low-dose group, liver tissue pathology of rats have only mild improvement.but in the betulin middle-dose group and height-dose group, liver tissue pathology of rats have obvious improvment,and compared with positive control group have no significant difference,complete hepatic lobules structure and liver sinus were seen, hepatic cells cable structure were clear,a few swelling cells, ballooning degeneration phenomenon were not seen.4.Effect of betulin on the alcoholic fatty liver disease rats serum ALT and ASTThe level of serum ALT,AST of the model group were significant higher than normal control group(P<0.05). The level of serum ALT,AST of betulin middle-dose group were significant lower than model group(P<0.05). The level of serum ALT,AST of betulin middle-dose group compare with positive control group have no significant difference(P>0.05).5. Effect of betulin on the alcoholic fatty liver disease rats hepatic tissue TGThe level of hepatic tissue TG of the model group were significant higher than normal control group(P<0.05). The level of hepatic tissue TG of the betulin middle-dose group and high-dose group were significant lower than model group(P< 0.05). The level of hepatic tissue TG of betulin high-dose group compare with positive control group have no significant difference(P<0.05).6.Effect of betulin on the alcoholic fatty liver disease rats plasma endotoxin and serum cotokine TNF-α,Ⅱ-1,IL-18The level of plasma endotoxin of model group were significant higher than normal control group(P<0.05). The level of plasma endotoxin of betulin each dose group were all significant lower than model group(P<0.05). Betulin each dose group compare with normal control group and positive control group,the level of plasma endotoxin have no significant difference(P>0.05).The protein level of serum cotokine TNF-α,IL-1,IL-18 of model group were all higher than normal control group(P<0.05). The protein level of serum cotokine TNF-α,IL-1,IL-18 of betulin low-dose group and TNF-a of betulin high-dose group were all lower than model group(P<0.05). The protein level of serum cotokine TNF-α,IL-18 of betulin low-dose group and high-dose group and IL-18 of middle-dose group compare with positive control group have no significant difference(P>0.05). The protein level of serum cotokine IL-1 of betulin low-dose group compare with normal control group have no significant dfference(P>0.05). 7.Effect of betulin on alcoholic fatty liver disease rats hepatic tissue expression of TNF-α,IL-1,IL-18,CD14,LBP mRNAIn the normal control group, the expression level of rats hepatic tissue TNF-α,IL-1,IL-18,CD14,LBP mRNA were very weak, the expression of rats hepatic tissue TNF-α,IL-1,IL-18,CD14,LBP mRNA were not detected. The expression level of hepatic tissue TNF-α,IL-1,IL-18,CD14,LBP mRNA of betulin low-dose group were all lower than model group(P<0.05). The expression level of hepatic tissue TNF-α,IL-18,CD14,LBP mRNA of betulin low-dose group compare with positive control group have no significant difference(P>0.05). and the expression level of hepatic tissue IL-1 of betulin low-dose group were lower than positive control group(P<0.05). The expression level of hepatic tissue LBP mRNA of betulin middle-dose group and TNF-α,CD 14 mRNA of high-dose group compare with positive control group have no significant difference(P>0.05).Conclusion:Adopt liquor gastric lavage method could successfully establish animal model of alcoholic fatty liver disease. Betulin middle-dose group (20mg/kg) and high-dose group (40mg/kg) could reduce steatosis degree of hepatic cells, improve lipid metabolism.repair demaged hepatic cells.reduce the level of serum ALT,AST and hepatic TGAnd. Betulin low-dose group (10mg/kg) improve body bowel function.reduce endotoxemia.restrain the activity of hepatic kuffer cells.reduce the expression level of mRNA and protein of cytokine(TNF-α,IL-1,IL-18). and restrain the release of cytokines,in order to restrain hepatocyte injury.necrosis and liver tissue fibrosis.Through the experiment research show that betulin have certain therapeutical effect on alcoholic fatty liver disease rats.
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