坎地沙坦改善高脂饮食大鼠胰岛素抵抗的效应

目的 研究血管紧张索Ⅱ受体1拮抗剂(ARB)--坎地沙坦改善高脂饮食诱导大鼠胰岛素抵抗的效应及其可能机制.方法 45只雄性Wistar大鼠随机分为普通饲料组(NC组,15只),高脂饲料组(HF组,15只)和高脂饲料坎地沙坦药物组(HF+C组,15只).HF+C组每天灌胃坎地沙坦西酯8 mg/kg,其他两组分别给予等量生理盐水.治疗4周后测定血清生化、胰岛素,进行口服葡萄糖耐量和高胰岛素-正常葡萄糖钳夹实验,评估坎地沙坦对胰岛素敏感性的影响.并用免疫组化法检测肝脏和脂肪组织过氧化物酶体增殖物活化受体γ(PPARγ)的表达.结果 HF组大鼠体重、肝脏、附睾及肾周脂肪重量均明显高于NC和HF+C组(均P<0.01),空腹血糖差异无统计学意义(P>0.05),但HF+c组葡萄糖负荷后2 h血糖明显低于HF组(6.3±0.5)mmol/L vs(7.3±1.2)mmol/L,P<0.01].钳夹结果显示HF+C组葡萄糖输入率明显高于HF组(22±5)mmoL/L vs(14±4)mmol/L,P<0.01].HF+C组肝脏和脂肪PPAγ蛋白表达水平明显高于HF组.结论 坎地沙坦可明显改善高脂饮食大鼠的胰岛素抵抗,肝脏和脂肪组织PPARγ的高表达.

Candesartan improves insulin resistance induced by high-fat diet in rots

Objective To investigate the effects of candesartan, an angiotensiou Ⅱ type Ⅰ receptor antagonist, in improvement of insulin resistance (IR) induced by high-fat diet and the possible mechanism thereof. Methods 45 male Wistar rats were randomly divided into 3 groups: normal chow group (NC, n= 15) fed with normal diet, high fat diet group (HF, n=15) fed with high fat diet, and high-fat diet with daily candesartsn treatment group (HF+C, n=15) fed with high fat diet and given orally with candesartan 8 mg/kg per day. Body weight was measured regularly. Four weeks later, oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp technique were performed to estimate the insulin sensitivity. After 12 h fasting blood samples were collected from the abdominal aorta to test the contents of blood glucose, and serum triglyceride (TG), total cholesterol (TC), LDL, HDL, and free fatty acid (FFA). Radioimmunoassay was used to detect the serum insulin. Viscera were taken out. Immunohistochemistry was used to examine the expression of peroxisome proliferation activated receptor (PPAR)-γ in hepatic and adipose tissues. Results The body weight 16 weeks later of the HF group was significantly higher than that of the HF + C group (P<0.01). The liver weight and epididymal and peri renal fat weights of the HF group were all significantly higher than those of the HF + C group and NC group (all P<0.01). There was no significant difference in fasting blood sugar among these 3 groups (P> 0.05). The glucose levels 2 h after OGTT in the HF + C group was (6.3±0.5) mmol/L, significantly lower than that of the HF group (7.3±1.2) mmol/L, P<0.01]. The glucose infusion rate (GIR) of the HF +C group was (22±5) mmol/L, significantly higher than that of the HF group (14±4) mmol/L, P<0.01]. The PPARγ expression levels in liver and adipose tissue of the HF + C group were up-regulated significantly compared with those of the HF group. Conclusion Candesartan may improve insulin resistance through promoting the expression of PPARγ in liver and adipose tissue.