ABSTRACT
AIM:To observe the effect of Tangshenfang(TS)on the liver protection and the levels of silent in-formation regulator 1(SIRT1)and peroxisom proliferator-activated receptor γcoactivator-1α(PGC-1α)in the liver tissue. METHODS:The rat model of diabetes mellitus(DM)was established by intravenous injection of streptozotocin(STZ;30 mg/kg)after having the high fat/high glucose diets for 1 month.The diabetic rats were randomly divided into DM group,DM with high-dose TS(TSHi)group, medium-dose TS(TSMed)group and low-dose TS(TSLow)group.The normal rats were served as control group.There were 8 rats in each group.After treatment with TS for 12 weeks,the serum biochemical indi-ces including fasting blood glucose(FBG), triglyceride(TG), alanine aminotransferase(ALT)and aspartate aminotrans-ferase(AST)were tested.Fasting insulin(FINS)was also detected by radioimmunoassay,and homeostatic model assess-ment for insulin resistance(HOMA-IR)was calculated.The serum levels of tumor necrosis factor-α(TNF-α)and interleu-kin-1(IL-1)were measured by ELISA.The activity of SOD and content of MDA in the liver tissues were measured by the methods of hydroxylamine and thiobarbituric acid.The liver pathological changes were observed under light microscope with HE and Masson staining.The protein expression of SIRT1and PGC-1αin the liver tissues was determined by Western blot. RESULTS:In DM group,serum FBG,TG,ALT,AST,FINS,HOMA-IR,TNF-αand IL-1 were obviously increased com-pared with the control group(P<0.01).The fatty changes,local necrosis,inflammation and fibrosis in the liver tissues were observed.The content of MDA in liver increased,while the activity of SOD decreased markedly.The protein expression of SIRT1 and PGC-1αwas decreased(P<0.05).In TS treatment groups,all these changes in DM rats were markedly reversed by TS,and the protein expression of SIRT1 and PGC-1αin the liver tissues was markedly increased.CONCLUSION:TS may protect the rats from diabetic liver injury by increasing the expression of SIRT 1 and PGC-1α,and thereby improving in-sulin resistance and oxidative stress.
ABSTRACT
OBJECTIVES@#To study the effects of ursolic acid on liver injury in diabetic mice induced by high-fat diet combined with streptozotocin(STZ), and to explore its possible mechanisms.@*METHODS@#Diabetes mellitus was induced in twenty male ICR mice by a combination of high-fat diet for 6 weeks with low-dose streptozotocin (30 mg/kg, i. p.) for 5 consecutive days. After 9 days, fasting blood glucose levels were determined. Mice with fasting blood glucose levels exceeded 11. 1 mmol/L were diagnosed as diabetic mice and selected for further experiment. These mice were randomly divided into two groups(each group of 10):diabetic group, ursolic acid group (100 mg/kg, i. g.), and another 10 mice were set as control group. After continuous administration for 8 weeks, body weight (BW) were weighed, fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate transaminase (AST) in serum and superoxide dismutase (SOD), malondialdehyde (MDA) in liver were measured. HE staining was used to observe pathological changes of liver tissue.@*RESULTS@#Compared with the control group, the level of FBG, TC, TG, ALT, AST, MDA were dramatically increased (<0. 05, <0. 01) and SOD was markedly decreased (<0.01) in the diabetic group; HE staining showed that parts of liver cells swelled and had a light fatty degeneration as well as lymphocyte infiltrated around the portal area in model group. Compared with the diabetic group, the level of FBG, TC, TG, ALT, AST, MDA were significantly declined (<0.05, <0.01) and SOD was considerably increased (<0.01) in the ursolic acid group; HE staining showed that the liver cells relatively arranged in order, edema was not obvious and inflammatory cells infiltrated lightly in the ursolic acid group.@*CONCLUSIONS@#Ursolic acid has a protective effect on liver injury in diabetic mice induced by high-fat diet combined with STZ by intraperitoneal ingector, and its mechanism may be associated with lowering blood glucose, regulating the lipid metabolism, reducing oxidative stress and enhancing the ability of anti-oxidation in liver.