ABSTRACT
Objective To evaluate the effects of telmisartan by SOCS-3/SREBP-1c pathway and its efficacy of improving insulin resistance (IR) in rats with high-fat diet-induced nonalcoholic steatohepatitis (NASH).Methods A total of 70 SD male rats were assigned randomly into 3 groups: A (normal control,20 rats,basic diet),B (model control,30 rats,high-fat diet) and C (treatment with telmisartan,20 rats,high-fat diet).After the IR-NASH model was made successfully,proved by 10 rats randomly from the group B with euglycemic hyperinsulinemic clamp technique (EHCT) and liver histology,the rats in the group C were intragastrically administrated telmisartan (5 mg/kg/d) for 4 weeks,and then all rats were tested with EHCT and sacrificed to test the blood chemistry,interleukin-6,homeostasis model assessment of insulin resistance,hepatic pathological analysis,and semiquantitative RT-PCR for determining SOCS-3 and SREBP-1c mRNA.Results Rats with high-fat diet developed steatohepatitis and insulin resistance at the 12th week and had more weight gain and higher liver index at the 16th week.IL-6,SOCS-3 and SREBP-1c mRNA expressions in the group B were up-regulated obviously,and each was positively correlated with the velocities of glucose infusion rates at 60~120 min.Blood chemistry and pathological observation in the group C were all improved;both SOCS-3 and SREBP-1c mRNA were down-regulated,and each negatively correlated with VGIR60-120,while serum IL-6 stayed at a high level.Conclusions Telmisartan can remarkably improve hepatic function and insulin resistance in rats with IR-NASH,the mechanisms of which would not be by path of reducing the secretion of IL-6,but by down-regulating the expressions of SOCS-3 and SREBP-1c mRNA.