The Preventive Effect Of3-MA, An Autophagy Inhibitor In Hepatic Fibrosis:a Mouse Model Study

Objective:Observing the effects of autophagy on heptaic fibrosis through3-methyl adenine of autophagy inhibitors in vivo and to expl-oring the feasibility of a new target autophagy signaling pathway as a treatment for liver fibrosis,in order to find a possible new way of treat-ment of heptaic fibrosis.Method:1. The70Balb/C mice were randomly divided into three groups. Model group and3-MA group were intraperitoneal injected with twenty percent of CC14and olive oil, a dose of2ml/kg, normal control group were injected with the same amount of olive oil, while3-MA prevention group were injected3-MA, a dose of15μg/g, a total8w,2times per week.2. The orbital venous blooding were detected ALT, AST, ALB in the eigth week.3. To use transmission electron microscopy observed autophagosome or autophagylysosome.4. To use the technol-ogy of immunohistochemistry analysised LC3-II and a-SMA.5. Liver biopsy specimens were objected to HE and Masson staining and observed fibrosis and collagen fiber distribution under an optical microscopeResults:1.The results of ALT, AST, TBIL have obviously signifi-cance between model and control groups.2.The control group had no significant vacuolization of mitochondria, and autophagosome. Model group showed obvious intracellular vacuolization of mitochondria, a large number of bilayer membrane structure autophagic vacuoles body,more than3-MA group.3. Model group and3-MA group LC3-II was signific-antly higher than the control group, and the model group was higher than3-MA, the differences among the three groups was statistically signi-ficant.4. The study found that the expression of a-SMA in the model group and the3-MA significantly was higher than the control group, the model group is highest, the differences among the three groups was statistically significant.5. Hepatic fibrosis of model group is more serio-us than3-MA group by the HE staining (p<0.05).6.In masson, the aver-age optical density and the total area of the liver tissue found that the model group was higher than3-MA group (p<0.05), the intervention group was higher than control group (p<0.05).Conclusion:1. The presence of autophagy proved that it involved in the formation of hepatic fibrosis in model induced by CC14.2. The3-MA can significantly inhibit on the development of the liver fibrosis.3. The3-MA achieved the purpose of inhibiting the development of hepatic fibrosis through reducing the level of autophagy inhibited the activation of hepatic stellate cells,suggesting that it has great prospects in the prevention of liver fibrosis fibrosis treatment.