Effects of telmisartan on nonalcoholic steatohepatitis rat model by activating peroxisome proliferator-activated receptor r

Abstract

To investigate the effects of telmisartan on steatohepatitis (NASH) in rats by activating peroxisome proliferator-activated receptor gamma (r). Thirty male SD rats were randomized into normal control group, NASH control group and telmisartan prevention group. Normal control group was given standard food and the other two groups were given high fat diet for 16 weeks to induce NASH. Prevention group was given telmisartan (5 mg.kg-1.d-1) for 4 weeks by intragastric adminstration after 12 weeks. At the end of the 16th week, all the rats were sacrificed. Pathological changes of liver were observed by optical microscopy. Serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), fasting blood glucose(FBG), fasting insulin(FINS), HOMA-IR(homeostasis model assessment insulin resistance), Serum TNF-a and adiponectin were detected and analyzed.Western blot and RT-PCR were used to detect PPARr expression in hepatic tissues on protein and mRNA levels. (1) Rats were successfully modeled. The liver tissue samples were divided into 4 degrees (F0 - 4) based on total fatty degeneration of liver cells.There was one rat reached F3 and nine rats reached F4 in NASH group, one rat reached F1, six rats reached F2 and three rats reached F3 in prevention group. Inflammatory activity scores of hepatic tissues in the model group were 2.67+/-0.25, while that in the control group was 0 (U=15 and P is less than to 0.01), in the prevention group were 2.67+/-0.25 and 1.36+/-0.12 (U=24 and P is less than to 0.05 ). (2) The levels of serum ALT, AST, FBG, FINS, TNFa and HOMA-IR in the model group were increased than those in the control group( the vaules of q were 13.130, 6.472, 6.909, 26.619, 14.591 and 49.683 respectively, P less than 0.01). The levels of serum ALT, FINS, FBG, TNFa and HOMA-IR in the prevention group were decreased as compared to the model group (the vaules of q were 7.024, 4.145, 14.829, 13.195 and 31.991 respectively, P less than 0.01 ). (3) The serum adiponectin, PPARrmRNA and protein in liver tissues of the model group were lower than those in the control group (q values were 10.696, 8.679 and 16.762 respectively, P is less than to 0.05).The data in the prevention group were higher as compared to the model group(q values were 3.879,3.079,6.400, P is less than to 0.05 respectively). HOMA-IR was positively correlated with the expression of TNFa but negatively correlated with the expression of adiponectin (r = 0.927, P is less than to 0.01; r = -0.891, P is less than to 0.01, respectively). Telmisartan may has preventive effect on rats with steatohepatitis (NASH) by a mechanism of activating peroxisome proliferator-activated receptor r.