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.
ABSTRACT
Objective To explore the effects of telmisartan on expression of peroxisome proliferators PPARs activated receptors and adiponectin receptor 2 in rats with nonalcoholic steatohepatitis (NASH).Methods Forty male SD rats were randomized into normal-diet control group (NC,n=15),high fat-diet control group (FC,n=15),and high fat-diet with telmisartan group (FT,n =10).NC group was given standard diet and the other two groups were given high-fat diet.At the end of the 12th week,5 rats which were randomly selected from both the NC and FC groups were given euglycermic hyperinsulinemia clamp to see if fat-liver model of rats with insulin resistance was successfully induced,and rat livers were removed for pathological examination to determine the extents of NASH.Afterwards,rats in the FT group was given telmisartan (5 mg/kg·d) while rats in both the NC and FC groups were given the same volume of 0.9% saline solution by intragastric gavage for another 4 weeks.After glucose infusion rates (GIRs) were obtained by the euglycermic hyperinsulinemia clamp technique at the end of the 16th week,all rats were sacrificed and the body weight was recorded,and serum lipids,aminotransferases and fasting blood glucose were measured.The mRNA expressions of peroxisome proliferator activated receptors (PPARs),adiponectin receptor-2 and angiotensin II type-1 receptor in the liver tissue were assessed by semi-quantitative reverse transcriptase polymerase chain reactions.Results The expressions of PPARα,PPARγ and AdipoR2 mRNA in the liver tissue of FC group were decreased significantly compared with the NC group (P<0.01),and the expression of AT1R mRNA of the liver tissue in FC group was increased significantly compared with NC group (P<0.01).Compared with the FC group,the expressions of PPARα,PPARγ and AdipoR2 mRNA in the FT group were increased (P<0.01).Serum aminotransferases,lipids and fasting blood glucose level in the rats of FC group were increased significantly compared with rats of the NC group (P<0.01),and serum aminotransferases,lipids and fasting blood glucose level in the rats of FT group were greatly improved compared with the FC group.Conclusions Telmisartan can improve glucose and lipid metabolism,stop weight gain,decrease liver index,and alleviate steatosis and inflammation of NASH rats by improving insulin resistance.Telmisartan may play an effective role in the protection of rat liver with NASH.