罗格列酮对胰岛素抵抗大鼠血一氧化氮和内皮素的影响

目的 探讨罗格列酮对胰岛素抵抗大鼠血一氧化氮和内皮素的影响及其可能作用机制。方法 采用高果糖饲料诱导SD大鼠建立胰岛素抵抗模型，并以普通饲料喂养作为对照组，4周后分别用与不用罗格列酮处理对照组和模型组。8周末测定各组收缩压、空腹血糖、血胰岛素、血脂、血清一氧化氮和血浆内皮素的含量及主动脉一氧化氮合酶活性。结果 模型组收缩压、血胰岛素和血浆内皮素均高于对照组；主动脉一氧化氮舍酶活性和一氧化氮含量显著低于对照组，同时出现脂质代谢紊乱。罗格列酮能显著降低模型组收缩压、血胰岛素和血浆内皮素；提高主动脉一氧化氮合酶活性和一氧化氮含量；改善胰岛素抵抗及脂质代谢紊乱，但罗格列酮不影响对照组大鼠上述各项指标。结论 罗格列酮能改善胰岛素抵抗大鼠血管内皮功能，其机制可能是：一方面通过降低血压、提高胰岛素的敏感性、改善脂质代谢紊乱；另一方面通过提高主动脉一氧化氮合酶活性促进主动脉一氧化氮释放，同时抑制内皮素的增加。

Effects of Rosiglitazone on the Levels of Nitric Oxide and Endothelin in Rats with Insulin Resistance

Aim To investigate the effect of rosiglitazone on the blood levels of nitric oxide(NO)and endothelin-1(ET-1) in insulin resistant rats and the underlying mechanism.Methods Male Sprague-Dawley(SD) rats were fed with high fructose to induce insulin resistant rats model,rats were treated with or without rosiglitazone after 4 weeks.At the end of 8th week,systolic blood pressure(SBP),fasting blood sugar(FBS),fasting serum insulin(FSI),blood lipids,NO,ET-1 and aortic nitric oxide synthase(NOS) activity were measured respectively in groups.Results Compared with control group,SBP,FSI and ET-1 in model group significantly increased;aortic NOS activity and NO levels were significantly lowered.At the same time,the abnormity of lipid metabolism appeared in the model group.After rosiglitazone treatment,SBP,FSI and ET-1 remarkably reduced;aortic NOS activity and NO levels significantly increased;insulin resistance and the abnormity of lipid metabolism were improved.While all indexes did not change significantly after rosiglitazone treated control rats.Conclusions Rosiglitazone may improve vascular endothelial function in rats with insulin resistance by decreasing blood pressure,increasing insulin sensitivity,improving the abnormity of lipid metabolism,besides,it could be associated with nitric oxide elevating by increasing nitric oxide synthase activity and inhibiting endothelin increasing.