替米沙坦上调胰岛素抵抗大鼠心肌脂联素及其受体的表达

Telmisartan upregulates expression of myocardial adiponectin and receptor in insulin-resistant rats

目的:探讨胰岛素抵抗(IR)大鼠心肌脂联素(APN)及其受体(AdipoR1和AdipoR2)表达改变和替米沙坦(TMST)的影响。方法:雄性SD大鼠50只随机选择10只作为对照组(用普通饲料喂养8周),其余40只大鼠用高果糖饮食喂养4周建立IR模型。从IR大鼠中随机选择10只作为IR组(用生理盐水灌胃4周,继续用高果糖饮食喂养);另选10只作为TMST组[用替米沙坦5 mg/(kg.d)灌胃4周,继续用高果糖饮食喂养]。所有大鼠均于喂养的第8周末,空腹采血,分别采用ELISA法和放射免疫法测定血清APN和肿瘤坏死因子-α(TNF-α)的水平。采用Western blot法测定各组大鼠心肌组织中APN、AdipoR1、AdipoR2、过氧化物酶体增殖物激活受体-γ(PPARγ)及TNF-α蛋白的表达。结果:实验第8周末,与对照组相比,IR组血清APN的水平降低(P<0.01)而血清TNF-α的水平升高(P<0.01)。大鼠心肌中APN、AdipoR1及PPAR-γ蛋白的表达降低(P<0.01);心肌中TNF-α蛋白的表达增高(P<0.01),而心肌中AdipoR2蛋白的表达无明显变化。与IR组大鼠相比,TMST组大鼠血清APN增高(P<0.05)而血清TNF-α水平降低(P<0.05),心肌APN、AdipoR1及PPAR-γ蛋白的表达增高(P<0.05);心肌中TNF-α蛋白的表达降低(P<0.05),而心肌中AdipoR2蛋白的表达无明显变化。结论:IR大鼠心肌中APN及Adi-poR1及PPARγ蛋白的表达降低;心肌中TNF-α蛋白的表达增高。TMST可通过激活PPARγ途径,增加循环中APN的水平,特别是激活心肌组织中的PPARγ,减轻炎症,提高APN及其受体的表达。

AIM： To explore expression of myocardial adiponectin and its receptors in insulin-resistant（IR） rats and to study the effect of telmisartan（TMST）.METHODS： Fifty male Sprague Dawley rats were included in the study,ten of whom were put in group C and were fed with ordinary diet for 8 weeks.The other 40 rats were fed with a high-fructose diet for 4 weeks to induce IR rat model.Ten IR rats were selected as IR group and were fed with high-fructose diet and treated with 0.9% saline for the next 4 weeks.Another 10 IR rats were selected as TMST group and were fed with high-fructose diet and treated with telmisartan 5 mg/（kg·day） for the next 4 weeks.After 8 weeks,blood samples were obtained and APN and TNF-α were measured.Protein expressions of myocardial APN,AdipoR1,AdipoR2,PPARγ and TNF-α were detected by Western blot.RESULTS： Compared with those in group C,serum APN decreased and TNF-α level increased in IR group.Compared with those in IR group,serum APN increased and serum TNF-α level decreased in TMST group.Protein expressions of myocardial APN,AdipoR1 and PPARγ were attenuated with enhanced TNF-α in IR group compared with those in group C.Protein expressions of myocardial APN,AdipoR1 and PPARγ were enhanced with attenuated TNF-α in TMST group compared with those in IR group.CONCLUSION： In IR rats,myocardial protein expressions of APN,AdipoR1 and PPARγ decreased and myocardial protein expressions of TNF-α increased.TMST can increase the myocardial expressions of adiponectin AdipoR1 and PPARγ and reduce inflammation.