Effects Of Probucol On Morphology And Thioredoxin Of Liver In Diabetic Fatty Liver Rats

Objectives 1) To observe pathological changes of livers in diabetic fatty liver rats and the expression of thioredoxin. 2) To investigate effects of Probucol on diabetic fatty liver rats and explore the possible mechanisms involved.Methods Forty male Wistar rats were randomly divided into normal control group (n=10,fed with normal food) and experimental group (n=30,fed with high-sugar and high-fat food). Four weeks later, streptozotocin(STZ 35mg/kg)was injected intraperitoneally to establish experimental diabetic rat models. Fatty liver rat models were proved to be successful by liver histology at the end of 9th week.Then the diabetic fatty liver rats were subdivided into model group (n = 11)and probucol intervention group (n=11). Probucol intervention group were treated with Probucol (500mg/d·Kg) by daily intragastric administration for 8 week.By the end of the 17th week, all rats were killed to test the level of fasting blood glucose (FBG), liver weight, liver Index, liver function, lipids, thioredoxin, oxidative stress parameters and liver histopathological changes.Results 1) After 4 weeks, characteristic changes of fatty liver, including enlarged liver, lipid deposition, fatty degeneration of liver cells, infiltration of inflammatory cells, were observed in diabetic rats fed with high-sugar and high-fat food for 4 weeks.2) By the end of the 17th week, the level of FBQwater consumption, ALT,AST, serum TG,serum TC, LDL, liver TQliver TC, liver weight, liver index,MDA, serum TRx, liver TRx expression, hepatic steatosis and infiltration of inflammatory cell score of model group were significantly higher than the normal control group (p<0.01).The level of HDL,SOD and SOD/MDA of model group was significantly lower than the normal control group (p<0.01).3) By the end of the 17th week, the level of liver weight, liver index, AST, ALT, liver TC, serum TC, fatty degeneration, inflammatory levels, LDL, MDA, serum TRx, the TRx expression of the liver of probucol intervention group were significantly Lower than the model group (p <0.01). SOD of probucol intervention group was significantly higher than the model group (p<0.05).4) Serum TRx content of the rats was negatively correlated with serum SOD content(γ=-0.954,p<0.001). Serum TRx content of the rats was positively correlated with serum MDA content(γ=0.820,p<0.001).Conclusions 1) Livers of diabetic fatty liver rats manifested with abnormal liver function, enlarged liver, liver lipid deposition, hepatic steatosis and infiltration of inflammatory cell and other pathological changes. And all pathological changes can be alleviated by 8 weeks' treatment of probucol, which suggests that probucol has therapeutic effects on diabetic fatty liver rats.2) Therapeutic effects of Probucol on diabetic fatty liver rats may be related to improvement of the oxidative stress state.3) Thioredoxin correlated with oxidative stress of the body of diabetic fatty liver rats.4) Oxidative stress exists in the livers of diabetic fatty liver rats, and probucol can improve oxidative stress of the livers.