【摘要】 目的　探讨游离脂肪酸 (FFA)是否可独立直接地导致内皮细胞功能异常以及增强胰岛素作用 ,能否缓解FFA所致的内皮功能异常。方法　将SD雄性大鼠 2 9只 ,分为 4组。对照组大鼠 5只经颈静脉插管输入生理盐水 ;FFA组 9只采用脂肪乳 +肝素静脉输注 ,升高血FFA水平 2～ 4倍 ;Ins组 5只用正常血糖高胰岛素钳夹技术输入短效胰岛素 ;FFA +Ins组 10只 ,在脂肪乳 +肝素静脉输注的同时用胰岛素钳夹技术输入胰岛素。输液结束后处死动物 ,取出主动脉置于器官池中 ,通过力转换器、放大器以及电子计算机记录主动脉环的张力 ,观察离体主动脉环对乙酰胆碱或硝普钠的舒张反应。结果　对照组及Ins组内皮依赖性血管舒张功能 (EDV)良好 ,FFA组EDV明显受损 ,FFA +Ins组EDV介于对照组与FFA组之间。各组动物非内皮依赖性血管舒张功能无明显差别。结论　由于循环中FFA水平升高可直接导致内皮细胞功能异常 ,因此推测FFA具有致动脉粥样硬化的作用 ,而升高血中胰岛素浓度有助于部分缓解FFA所致的内皮依赖性血管舒张功能异常。更多还原

【Abstract】 Objective To investigate whether free fatty acid (FFA) directly and independently causes endothelial dysfunction and whether enhancing insulin action mitigates FFA induced endothelial dysfunction. Methods Twenty nine S D rats were divided into 4 groups and infused by jugular catheterization with different solutions: 20% intralipid +heparin (0.72 IU/min) for 4 hours (FFA group, n =9), short acting insulin by hyperinsulinemic euglycemic clamp for 4 hours (Ins group, n =5), intralipid +heparin and insulin by hyperinsulinemic euglycemic clamp for 4 hours (Ins+FFA group, n =10), and normal saline (18μl/min) for 4 hours(C group, n =5). After the infusion, the rats were killed and their aortic rings were resected and put into organbath and connected to a force trranducer and amplifier. PGF2a was added into the organbath to constrict the rings until the constriction tension reached a balance. Then acethylcholine (Ach) and sodium nitroprusside (SNP) of increasing concentrations were added to relex the rings to record the endothelial dependent vasodilatation (EDV) and endothelium independent vasodilatation (EIV). Results The EDV value was 85 0%±3 2% in C group and 54 8%±2 5% in FFA group (C vs FFA, P =0 002); 80 6%±1 8% in Ins group (C vs Ins, P =ns); 72 8%±2 1% in Ins+FFA group (FFA+Ins vs C P =0 02,FFA+Ins vs FFA, P =0 005). The EIV response in the three experimental groups was not different from that in the control group. Conclusion FFA damages the endothelisal depandant vasodilatation of aorta, thus causing endothelial dysfunction by direct interaction with the endothelium. FFA may be proatherogenic. Hyperinsulinemia has salutary effects on endothelial function in the context of elevated FFA.更多还原