胰岛素介导的内皮依赖性血管舒张功能与高血糖关系的实验研究

An experimental study of the relationship between hyperglycemia and insulin-mediated endothelium-dependent vasodilation

目的 研究不同浓度胰岛素、葡萄糖对培养血管内皮细胞一氧化氮 (NO)产生的影响 ,探讨糖尿病时内皮依赖性血管舒张异常的作用机制。方法 用放免法测定内皮细胞cGMP水平来反映NO的量 ;半定量RT PCR检测NO合酶 (eNOS)mRNA水平。结果 胰岛素 (0 .18～ 6 .0nmol/L)、葡萄糖 (2 0mmol/L ,40mmol/L)能增加内皮细胞cGMP产量 ,并呈浓度和时间依赖性 ;高浓度葡萄糖上调eNOSmRNA水平 ,而胰岛素对其无影响 ;在高浓度葡萄糖下 ,胰岛素 (6 .0nmol/L)刺激NO的生成作用明显降低。结论 胰岛素介导的内皮依赖性血管扩张与胰岛素刺激内皮细胞NO合成有关 ;血管内皮对胰岛素的敏感性减低是胰岛素抵抗的一部分 ;高浓度葡萄糖可能会抑制胰岛素介导的内皮依赖性血管舒张。

Objective To investigate the effect of various concentrations of glucose and insulin on nitric oxide (NO) production of vascular endothelia in culture and to explore the mechanism of abnormal endothelium-dependent vasodilation in diabetics. Methods cGMP radioimmunoassay for endothelium cells was used in this study as an indicator of NO production, and the level of eNOS mRNA was measured by semiquantitative RT-PCR. Results Insulin (0.18～6.0 nmol/L) and glucose (20 mmol/L, 40 mmol/L) could stimulate cGMP production which is concentration- and time- dependent. High concentration of glucose upregulated the level of eNOS mRNA, insulin had no effect on the expression of eNOS. At higher glucose concentration, NO production stimulated by insulin (6.0 nmol/L) was significantly decreased. Conclusion Endothelium-dependent vasodilation induced by insulin is associated with endothelial NO production. Decreased sensitivity of endothelium to insulin is a part of insulin resistance. High concentrations of glucose probably inhibit insulin-mediated endothelium-dependent vasodilation.