2型糖尿病大鼠血管内皮功能改变及机制

Change of Aortic Endothelium-dependent Vasodilation Function in Type 2 Diabetic Rats and its Mechanism

目的探讨2型糖尿病大鼠胸主动脉内皮依赖血管舒张功能的改变及其机制。方法高脂高糖饮食加小剂量链脲佐菌素建立2型糖尿病大鼠模型,分组处理4周后,观察糖尿病(DM)组、正常(NC)组、糖基化终末产物抑制剂(AG)组血管舒张功能,eNOSmRNA表达及血清NO浓度。结果①DM组血糖、血清胰岛素、甘油三酯较NC组显著升高(P<0.05)。②最大内皮依赖血管舒张功能(EDVRmax),DM组低于AG组(P<0.05),AG组低于NC组(P<0.05)。③eNOSmRNA表达,AG组高于DM组(P<0.05),DM组高于NC组(P<0.05)。④血清NO浓度AG组高于NC组(P<0.05),NC组高于DM组(P<0.05)。结论高级糖基化终末产物(AGEs)通过NO途径介导糖尿病内皮功能损伤,糖基化终末产物抑制剂(AG)可改善内皮依赖血管舒张功能。

Objective To study the change of aortic endothelium-dependent vasodilation function in type 2 diabetic rats and its mechanism. Methods Male SD rats were injected with low dose Streptozotocin and fed with diets enriched in fat and sugar to form type 2 diabetic model. Then, the rats were managed in 3 groups, normal group （ NC）, diabetes group （ DM ）, diabetes with Aminoguanidine（AG） group. After 4 weeks, the Ach-dependent vasodilation response of isolated aorta, the expression of eNOS mRNA in the aorta, the synthesis of nitric oxide（NO） in serum were detected. Results ① Fast plasma glucose（ FPG）, insulin （ FINS）, triglyceride （TG） levers in DM groups were significantly higher than that in NC groups （ P 〈 0. 05 ）. ② The maximum acetylcholine（Ach）-dependent vasodilation response （EDVRmax） of aorta decreased significantly in DM, AG groups compared with that in NC groups （ P 〈 0. 05 ） ; EDVRmax in DM groups significantly reduced than that in AG groups （P 〈 0. 05 ）. ③The eNOS mRNA expression in DM groups were significantly higher than that in NC groups （ P 〈 0. 05 ）, but lower than that in AG groups （ P 〈 0. 05 ）. ④ NO concentration were significantly higher in AG groups （ P 〈 0. 05 ） ; but those in DM groups were significantly lower than that in NC groups （P 〈 0. 05）. Conclusion Advanced glycation end products （AGEs） damaged the function of vascular endothelium though nitric oxide pathway and inhibitor Aminoguanidine（AG） can get an improved EDVR.