Effects Of Rosiglitazone Combined With Reduced Glutathione On Insulin,IR,IRS-2 And Biochemical Indicators In NAFL Rats

Objective:To produce NAFL model by improvement high-fat-diet. To compare liver biochemical indicators in model group with normal group, and investigate effects of rosiglitazone and reduced glutathione on biochemical indicators. To compare insulin,IR,IRS-2 in serum and pancreatic tissue of model group with normal group, and investigate effects of rosiglitazone and reduced glutathione on insulin,IR,IRS-2.Methods: 40 rats were randomly divided into four groups:normal group ,model group ,rosiglitazone group, group of rosiglitazone combined with reduced glutathione. The control group rats were fed with normal diet,and the other three groups were fed with high-fat-diet.At the same time,the drug group were treated with rosiglitazone combined with reduced glutathione. 8 weeks later, NAFL rats were produced. The insulin, insulin receptor(IR) and insulin receptor substrate-2(IRS-2) in serum and pancreatic tissue were detected by hematoxylin-eosin(HE) staining, immunohistochemisty and ELISA ,and the biochemical indicators were detected at the same time. Then their content or intensity were compared among the above groups.Results:1,NAFL rats were produced. Abdominal part CT of model group rats showed that the CT value of liver is lower than pleen. And histopathology showed fat deposition in liver cell. 2,The level of albumin, ALT, total cholesterol increased obviously compared with normal group(P<0.01), but the concentration of triglyceride and fasting blood glucose in model group decreased markedly(P<0.01). The level of AST,total cholesterol,T.bilirubin in rosiglitazone group decreased than these in model group(P>0.05). 3, The serum insulin level of model group increased obviously compared with normal group(P<0.01), but the concentration of IR and IRS-2 in model group decreased markedly(P<0.01); The serum insulin levels of drug intervention groups were down-regulated obviously(P<0.05); The serum IR level of rosiglitazone group increased significantly compared with model group and combined treatment group (P<0.05), but the level of IRS-2 occurred no significant difference compared among model group and treatment groups. 4,The insulin expressing level in pancreas of model group was obviously higher than that of normal group(P<0.05); The insulin expressing levels of drug intervention groups were more lower that of model group(P<0.05) , but the levels of IR and IRS-2 in drug intervention groups were higher than that of model group(P<0.05).Conclusions:1,NAFL model were produced successfully. 2,The biochemical indicators(albumin, triglyceride ,ALT, fasting blood glucose ,total cholesterol) in NAFL rats changed significantly, and the existence of insulin resistance were Obviously. The Rosiglitazone and Reduced Glutathione can reverse the level of biochemical indicators,decrease the insulin resistance index,but there is no difference between the two treatment groups.3,The concentrations of insulin, IR and IRS-2 in sera and pancreas of NAFLD rats occur remarkable change; Rosiglitazone alone and combined with reduced glutathione might down-regulate the insulin levels in sera and pancreatic tissue of model group and up-regulate, to some extent, the concentrations of IR and IRS-2 of model group, but combined treatment occurs no cooperative effects.