坎地沙坦对自发性高血压大鼠骨骼肌胰岛素敏感性的影响

Effect of candesartan on insulin sensitivity in skeletal muscle of spontaneous hypertensive rats

目的探讨血管紧张素Ⅱ(AngⅡ)受体拮抗剂(ARB)坎地沙坦对自发性高血压大鼠(SHR)骨骼肌胰岛素敏感性的影响及其机制。方法 30只SHR随机分为模型组、坎地沙坦高剂量组(Can 1组)及坎地沙坦低剂量组(Can 2组),每组10只,另选10只WKY大鼠作为对照组。均给予果糖喂养,Can 1组(0.8 mg/kg)、Can 2组(0.4mg/kg)分别给予坎地沙坦灌胃干预,观察第8周末各组大鼠胰岛素抵抗指数(HOMA-IR)和AngⅡ的水平,以及骨骼肌蛋白激酶B(Akt)的基因及蛋白表达水平。结果与对照组比较,模型组大鼠AngⅡ、HOMA-IR及血清空腹胰岛素(FINS)明显升高,骨骼肌中Akt mRNA表达及P-Akt蛋白表达显著减少,差异有统计学意义(P<0.05,P<0.01)。与模型组比较,Can 1组大鼠FINS、HOMA-IR明显降低,Can 1组和Can 2组骨骼肌Akt mRNA表达及P-Akt表达显著增加,差异有统计学意义(P<0.05,P<0.01)。结论 AngⅡ通过下调SHR骨骼肌的Akt蛋白表达引起胰岛素抵抗,而坎地沙坦通过抑制AngⅡ的这种作用改善骨骼肌胰岛素抵抗。

Objective To study the effect of candesartan on insulin resistance in skeletal muscle of spontaneously hypertensive rats （SHR） and its mechanism. Methods Thirty SHR were randomly divided into model group, high dose candesartan group and low dose candesartan group （10 in each group） and 10 WKY rats served as a control group. The animals were fed with fructose. Eight weeks after the rats in high dose candesartan group and low dose candesartan group received gastric candesartan treatment at the dose of 0.8 mg/kg and 0.4 mg/kg,respectively,their insulin re sistance index, serum Ang Ⅱ level, and protein kinase B （Akt） gene and protein expression level were measured,respectively. Results The serum Ang Ⅱ level,insulin resistance index and serum insulin level were significantly higher while the Akt mRNA and protein expression levels were significantly lower in model group than in control group （P〈0.05,P〈0.01）. The insulin resist- ance index and serum insulin level were significantly lower in high dose candesartan group than in model group while the Akt mRNA and protein expression levels were significantly higher in high dose candesartan group and low dose candesartan group than in model group （P〈0. 05, P〈0.01）. Conclusion Ang Ⅱincreases the insulin resistance by down-regulating the Akt mRNA and protein expression in skeletal muscle of SHR while candesartan decreases the insulin resistance by inhibiting the effect of Ang Ⅱ on insulin resistance in skeletal muscle of SHR.