Effects Of Shenling Baizhu Powder On Mitochondrial Energy Metabolism In NAFLD Mice

Objective:To replicate a high-fat diet-induced NAFLD mouse model and observe the regulatory effects of Shenling Baizhu powder on mitochondrial membrane function,mitochondrial respiratory status,adenylate content and mitochondrial energy metabolismrelated UCP2/AMPK/ IF1 signaling pathway proteins in NAFLD liver,and to investigate the mechanism of action of Shenling Baizhu powder in the treatment of NAFLD.Methods:Ninety-six SPF C57BL/6 mice(20±2g)were randomly divided into normal,model,melbine,Shen-low,Shen-medium and Shen-high groups,with 16 mice in each group.The normal group was fed with normal diet and the other groups were fed with high-fat diet.100 ml/kg of saline was administered to the normal and model groups,0.468 g/kg of metformin was administered to the metformin group,and 1,2 and 4 times the clinical equivalent of Shenling Baizhu powder was administered to the Shen low,medium and high groups at the end of 4-10 weeks(2.34 g/kg,4.68 g/kg,9.36g/kg).At the end of 8 and 10 weeks respectively,8 animals were taken from each group each time,and blood was taken for serum biochemical assay,and liver was taken for pathology,mitochondrial membrane permeability,mitochondrial respiratory status,adenosine content and mitochondrial UCP2,AMPK and IF1 protein expression.Results:1.Therapeutic effects of Shenling Baizhu powder on mice with high-fat dietinduced NAFLD: The body weight of mice in the model group increased significantly compared with the normal group at the end of 8 and 10 weeks,the liver color of the model group turned yellow and the liver-to-body ratio increased,each drug group could reduce the body weight and liver-to-body ratio of mice with NAFLD,and the values were between the normal and model groups.The HE staining results showed that the arrangement of liver cords in the model group was disordered,and the results of the oil red O staining showed that the arrangement of liver cords and the structure of liver lobules in the model group were restored,and the degree of hepatocyte steatosis and the number of fat particles deposited in the hepatocytes were significantly reduced.The biochemical indexes showed that ALT,AST,TBIL,FBG,TC,TG and LDL-C were lower and HDL-C was higher in the model group compared with the normal group(P<0.05).ALT,AST,TBIL,FBG,TC,TG,LDL-C were all higher and HDL-C was lower in each group of Shenling Baizhu powder than in the model group(P<0.05).2.The results of mitochondrial membrane permeability and oxidative phosphorylation function-related indexes: At the end of 8 and 10 weeks,the liver mitochondria in the model group had reduced sensitivity to high calcium solution and decreased membrane potential;total protein content was reduced,ST4 was increased,ST3,RCR,P/O and OPR were reduced,and adenylate content was reduced(P<0.01).Compared with the model group,the sensitivity of liver mitochondria to high calcium solution was increased and membrane potential was restored at the end of 8 and 10 in all other dosing groups;total protein content was increased,ST4 was decreased,ST3,RCR,P/O and OPR were increased(P<0.01);ATP was significantly increased at the end of 8 in the sensual low and sensual middle groups(P<0.01)and at the end of 10 in the diamorphic group(P<0.05).3.The results of UCP2,AMPK and IF1 in the liver: compared with the normal group,UCP2 was significantly increased,AMPK and IF1 were significantly decreased in the model group at the end of 8 and 10 weekends(P<0.01);compared with the model group,the UCP2 protein content was decreased in the sensual low and sensual middle groups at the end of 8 and 10weekends(P<0.05),and significantly decreased in the diatomic group(P<0.01);at the end of 8 and 10 weeks,ATP was significantly increased in the diatomic group(P<0.01).The AMPK content was significantly higher in both the diatomic group and the sensual high group at the end of 8 and 10 weeks(P<0.01);the IF1 content was higher in the sensual high group at the end of 8 weekends(P<0.05),and significantly higher in the sensual low,sensual middle and sensual high groups at the end of 10 weeks(P<0.01).Conclusion:1.The classical prescriptions of invigorating spleen,Shenling Baizhu powder can reduce liver lipid deposition in mice with non-alcoholic fatty liver disease induced by high-fat diet and play the role of invigorating spleen and disperse the liver.2.Shenling Baizhu powder can improve liver mitochondrial membrane permeability,respiratory status,oxidative phosphorylation efficiency and increase liver ATP content in mice with non-alcoholic fatty liver disease,and can regulate the UCP2/AMPK/IF1 signaling pathway of liver mitochondrial energy metabolism,which affects mitochondrial function and plays a role in supplementing Qi and disperse the liver.