替米沙坦对非酒精性脂肪肝大鼠肝组织PPARs及脂联素受体2表达的影响

Effects of telmisartan on the expressions of PPARs and adiponectin receptor2 in the liver tissue of rat with nonalcoholic steatohepatitis

目的探讨替米沙坦对非酒精性脂肪肝大鼠肝组织PPARs及脂联素受体2表达的影响。方法 40只雄性SD大鼠随机分为正常对照组(NC,n=15)、高脂对照组(FC,n=15)、高脂+替米沙坦干预组(FT,n=10)。NC组给予普通饲料,FC和FT组予高脂饲料喂养。12周末时随机取NC组和FC组各5只做正葡萄糖高胰岛素嵌夹实验和肝组织HE染色,确定造模成功后,FT组给予替米沙坦5 mg/(kg·d)灌胃,NC和FC组以等容量生理盐水灌胃,共4周。16周时应用高胰岛素正葡萄糖嵌夹实验技术稳态葡萄糖输注速率测定胰岛素敏感性,检测血清转氨酶、血脂及空腹血糖水平;应用逆转录聚合酶链反应法测定肝组织中过氧化物本酶体增殖活化受体(PPARs)、脂联素受体2(AdipoR2)和血管紧张素II 1型受体(AT1R)的表达。结果与NC组相比,FC组肝组织PPARα、PPARγ、AdipoR2 mRNA表达显著下降(P<0.01),AT1R mRNA表达较NC组升高(P<0.01);FT组PPARα、PPARγ、AdipoR2 mRNA表达较FC组升高(P<0.01);FT组血清转氨酶、血脂及空腹血糖水平较FC组改善。结论替米沙坦能降低NASH大鼠的体重和肝指数,调节糖脂代谢并改善胰岛素抵抗状态,对NASH大鼠肝脏具有保护作用。

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.