Experimental Research Of Jiangzhi Yigan Chongji On The Prevention And Treatment In Rats With Nonalcoholic Fatty Liver Disease

Objective:NAFLD is a genetic-environmental-metabolic stress-related disease,and it associated with insulin resistance,metabolic syndrome and is closely related to the genetic susceptibility.The "double impact" theory thought insulin resistance and oxidative stress/lipid peroxidation is the pathogenesis of the two key factors.Hence,current medical literature of NAFLD all focus on insulin resistance and lipid peroxidation.First,insulin resistance is the trigger factors in NAFLD,and lipid metabolism disorders is the initiation.Because simple fatty liver is a benign reversible disease,it is important that improving the insulin sensitivity and correcting lipid metabolism disorders by effective treatments for early prevention of NAFLD. When damages by oxidative stress in hepatocyte exceed its own defense capabilities,simply fatty liver will change to nonalcoholic steatohepatitis(NASH).Furthermore,NAFLD progress to cirrhosis must through the intermediate stages of non-alcoholic steatohepatitis.Therefore taking active treatment on NASH would effectively control the development of liver cirrhosis and liver cancer,and improve the prognosis of NAFLD.Current research shows that PPARαplays an important role in lipid metabolism and inflammatory responses,by modulateing the expressions of fatty acid oxidation and inflammatory.Its functional defects can not only induce steatosis,but also closely relate with NASH,cirrhosis and hepatocellular carcinoma.Recently,it has been recognized that Trx has close relation with the severity about NAFLD,also with the trans-graduation of PPARα.This experiment was designed to investigate the expression of peroxisome proliferators activated receptor(PPARα)and thioredoxin(Trx)in the liver of rats with nonalcoholic fatty liver disease(NAFLD)induced by high-fat diet and to explore their role and relevance in the development of NAFLD.And investigate the pharmacodynamic action and mechanisms about preservation and cure with treatment of JYG in NAFLD rat.Methods:56 Wistar rats were randomly divided into seven groups:normal control group(N),model groupⅠ(M1),model groupⅡ(M2),model GroupⅢ(M3)and traditional Chinese medicine groupⅠ(D1),traditional Chinese medicine groupⅡ(D2),traditional Chinese medicine groupⅢ(D3),each group has eight rats.All of the groups were fed with high-fat diet except normal group.Results:After eight weeks,the group M1 show to be abdomen-form obesity,developed lipid metabolism disorder accompanied with hyperinsulinemia and insulin resistance,increase of aminotransferase,tumor necrosis fator a in serum,the activity of SOD and MDA in liver has no difference with group N(P＞0.05);hepatocyte steatosis shown in hepatic histopathology.It tells insulin resistance play an key function at the beginning of NAFLD,but oxidative stress has no function at this stage.Compared with the grope N the expression of PPARαmRNA of group M1 and group D1 increased obviously,especially group D1(P＜0.05&P＜0.01),the expression of Trx mRNA decreased obviously.At this time PPARαmRNA and Trx mRNA has no relationship though correlation analysis.The blood serum and the contents of lipid in hepatic tissue of grope D1 had improved obviously compared with group M1,then the insulin sensitivity index which reflect insulin resistance also increased significant compared with group M1.The TNF-α, aminotransferase and the contents of MDA decreased significant compared with group M1,the expression of PPARαmRNA about hepatic tissue increased(P＜0.01 &P＜0.05),the extent about hepatic tissue sulfatide obviously relieved.At the beginning of the experiment group D1 were given high-fat diet while intragastric administration with traditional Chinese medicine for eight weeks,and killed with group N and group M1 at the end of eight week.Group D2 were given high-fat diet for eight weeks and then intragastric administration with traditional Chinese medicine for five weeks and killed with group M2 at the end of thirteen week.Group D3 were given high-fat diet for thirteen weeks and then intragastric administration with traditional Chinese medicine for five weeks and killed with group M3 at the end of eighteen week.After 13 weeks,the rats of group M2's insulin resistance,the contents of lipid in hepatic tissue and blood-fat,the contents of TNF-αin blood serum and aminotransferase increased obviously compared with group N.The contents of MDA in hepatic tissue obviously increased, archaeus of SOD obviously decreased.Hepatocyte steatosis developed and liver presented the pathology of inflammation cell infiltration and sporadic punctiform necrosis,the inflammation score in model group were increased significantly compared with normal group(P＜0.01).It tells oxidative stress play an key function in the progress of hepar steatosis.Compaired with group M1,the expression of PPARαmRNA in group M2 has a little decreased,but it still higher than group N and the difference has no statistics nuance.(P＞0.05).The expression of Trx mRNA about hepatic tissue also increased obviously compaired with group M1,but it is still below than group N.Then the correlation analysis about PPARαmRNA and Trx mRNA indicated the two issue has inverse correlation(γ=-0.802,P＜0.05).Lipid metabolism disorder and insulin resistance of the group D2 were improved,and the levels of aminotransferase, TNF-αin serum decreased significantly,MDA content decreased,SOD activity increased significantly,the expression of Trx mRNA in liver was increased,steatosis and inflammation of liver show significant improved compared with group M2.After 18 weeks,the rats of group M2's insulin resistance,the contents of lipid in hepatic tissue and blood-fat,the contents of TNF-αin blood serum and aminotransferase increased obviously compared with group N.The contents of MDA in hepatic tissue obviously increased, archaeus of SOD obviously decreased.The diffuse hepatocyte steatosis and ballooning degeneration of hepatic tissue,inflammation and extend of necrosis all exceed the group M2 at the 13 weekend.The expression of PPARαmRNA about hepatic tissue increased obviously compaired with group M2,but it is still below than group N.Then the correlation analysis about PPARαmRNA and Trx mRNA indicated the two issue has inverse correlation(γ=—0.82, P＜0.05).Lipid metabolism disorder and insulin resistance of the group D3 were improved,and the levels of aminotransferase,TNF-αin serum decreased significantly,MDA content decreased,SOD activity and ISI value increased significantly,the expression of Trx mRNA in liver was increased,steatosis and inflammation of liver show significant improved.Conclusion:1.Insulin resistance and oxygen stress/lipid peroxidation are two key factors in NAFLD.2.The reduce of expression of PPARαmRNA plays an important role in process of NAFLD.3.Negative autoregulation of PPARαactivity by Trx may closely relate to the occurrence of NASH.4.JYC can prevent the occurrence of simple fatty liver,and it can cure simply fatty liver and NASH.The mechanism maybe the increased expression of PPARαmRNA.