罗格列酮对2型糖尿病大鼠主动脉内皮依赖性血管舒张功能的影响

Effects of rosiglitazone on endothelium-dependent vasodilation function of aorta in type 2 diabetic rats

目的观察2型糖尿病(T2DM)大鼠胸主动脉内皮依赖性血管舒张功能和一氧化氮(NO)、一氧化氮合酶(eNOS)的变化及罗格列酮(RSG)治疗对其内皮功能的影响。方法SD大鼠经高糖高脂喂养6周后予小剂量链脲佐菌素腹腔注射建立T2DM大鼠模型,糖尿病大鼠又分为对照(DM)组和RSG治疗组,RSG组用RSG干预8周,另选正常大鼠为正常对照(NC)组。实验终止时用正常葡萄糖高胰岛素钳夹技术的葡萄糖输注率(GIR)评价胰岛素抵抗,观察大鼠离体主动脉内皮依赖性血管舒张反应和主动脉NO、eNOS的变化。结果T2DM大鼠GIR、胸主动脉内皮依赖性血管舒张反应、主动脉NO含量及eNOS阳性表达较NC组显著降低(P<0.01),RSG治疗后上述指标均显著升高(P<0.05)。结论T2DM大鼠存在内皮依赖性血管舒张功能紊乱,RSG治疗可改善内皮功能,增强NO水平和eNOS的活性。

Objective To observe the change of endothelium - dependent vasodilation of aorta and nitric oxide（NO） level and endothelial nitric oxide synthase（eNOS） activity, and the effects of rosiglitazone on those indexes in type 2 diabetic rats. Methods Type 2 diabetic rat model was established in 4 - 6 weeks-old SD rats by intraperitoneal injection of low dose streptozotocin after high glucose and high fat diet for 6 weeks. Diabetic rats were randomly divided into control group and treatment group（ DM vs RSG ）, and nor- mal rats were used as NC group. Rats of RSG group were given rosiglitazone 3 mg · kg^-1 · d^-1 for 8 weeks. IR was evaluated by glucose infusion rate （GIR） of euglycemic hyperinsulinemic clamp technique at the end of trial. The acetylcholine（Ach）-dependent vasodilation response, NO level and eNOS activity were observed in isolated aorta of rats. Results GIR, Ach - dependent vasodilation response , NO level and positive ex- pression of eNOS of isolated aorta were lower（ P 〈0.01 ） in DM group than in NC group, but those indexes were higher singnificantly （ P 〈 0.05） in RSG group than in DM group. Conclusion There is endotheli- um- dependent vasodilation dysfunction in type 2 diabetic rats. Treatment with rosiglitazone can improve en- dothelial function and increase NO level and eNOS activity.