替米沙坦对改善OLETF大鼠胰岛素抵抗作用的探讨

摘要

目的:研究血管紧张素Ⅱ1型(AT1)受体阻滞剂替米沙坦对改善OLETF大鼠胰岛素抵抗(IR)的作用.方法:OLETF大鼠47只,高脂喂养14周诱导建立IR大鼠模型并将其随机分为5组:IR对照组(IR组)、二甲双胍(MET)组、吡格列酮(P)组、替米沙坦(L)组、低剂量替米沙坦(VL)组,12只LETO大鼠为正常对照(NC)组.干预26周后测定空腹胰岛素(FINS)、游离脂肪酸(FFA)、网膜素、视黄醇结合蛋白4(RBP4)、内脂素、空腹血糖(FBG)及血脂,计算胰岛素抵抗指数(IIOMA-IR)和胰岛素敏感性指数(ISI).结果:L组较IR组的血清网膜素、ISI升高(P＜0.05或P＜0.01);RBP4、内脂素、FBG、HOMA-IR、TC、LDL-C和FFA降低(P＜0.05或P＜0.01).多元线性逐步回归分析显示网膜素、ISI是RBP4水平的影响因素；网膜素、HOMA-IR是内脂素水平的影响因素.结论:替米沙坦可能通过提高血清网膜素、降低血清RBP4和内脂素调节血脂水平,从析改善IR.%Objective:To investigate the mechanism and effect of angiotensin II type 1 (AT1) receptor blocker telmisartan in OLETF rats with insulin resistance (lR). Methods: Forty-seven male OLETF rats were fed with high-fat diet for 14 weeks to establish the insulin resistance model, and rats were randomly assigned into five groups, IR model group, metformin (MET) group, the pioglitazone (P) group, the telmisartan (L) group and low-dose telmisartan (VL) group. Twelve LETO rats fed with normal diet served as the normal control (NC) group. The serum levels of fasting insulin (FINS), free fatty acids (FFA), omentin, retinol binding protein 4 (RBP4), visfatin, plasma level of fasting blood glucose (FBG) and blood lipid were detected after 26 weeks treatment. The insulin resistance index (HOMA-IR) and insulin sensitivity index(Isl)were calculated. R9-sultS: Compared with group IR, the serum omentin and ISI were significantly higher in L group (P < 0.01 or P < 0.05), and the serum RBP4, visfatin, FBG, HOMA-IR, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and FFA were significantly decreased (P < 0.01 or P < 0.05). The multiple linear stepwise regression analysis showed that the serum omen-tin and ISI were significant determinant of RBP4, and the serum omentin and HOMA-IR were significant determinant of visfatin. Conclusion: Telmisartan can improve insulin resistance by inhibiting the expression of retinol binding protein 4 and visfatin, enhancing the expression of omentin and regulating lipid level.