高胆固醇血症对家兔主动脉内皮依赖性舒张功能的影响及机制研究

Effects of Hypercholesterolemia on Endothelium-Dependent Relaxation and Their Mechanisms

目的 :探讨高胆固醇血症对动脉内皮依赖性舒张功能的影响及前列腺素类物质在其中的作用。 方法 :新西兰兔 40只 ,随机分为 3组 :普通饮食组、高胆固醇组和阿司匹林组 ,观测离体胸主动脉乙酰胆碱(Ach)诱导的舒张反应及凝血烷A2 (血栓素A2 ,TXA2 )和前列环素 (PGI2 )代谢产物—凝血烷B2 (血栓素B2 ,TXB2 )及 6 酮 前列腺素F1α的生成。为观测TXA2 受体拮抗剂SQ2 954 8对动脉舒张功能的影响 ,将普通饮食组及高胆固醇组又各分为对照动脉和SQ2 954 8动脉。 结果 :高胆固醇组动脉Ach诱导的舒张功能较普通饮食组和阿司匹林组减弱 ,有显著性差异 (P <0 0 5 ) ;TXA2受体拮抗剂SQ2 954 8显著改善高胆固醇组动脉Ach诱导的舒张功能障碍 ;Ach刺激状态下 ,高胆固醇组有内皮动脉TXB2 的生成显著高于普通饮食组动脉 ,去内皮后这种差异丧失 ;高胆固醇组与普通饮食组动脉 6 酮 前列腺素F1a的生成无显著差异。 结论 :①高胆固醇血症引起的动脉舒张功能障碍与其增加内皮TXA2 的生成有关。②小剂量阿司匹林可改善高胆固醇血症引起的内皮依赖性舒张功能异常。

Objective:To explore the effects of hypercholesterolemia on the vascular endotheliumdependent relaxation and their mechanisms. Methods:Forty male New Zealand white rabbits were randomly divided into three groups:the control group?the cholesterol group and aspirin group.The endothelium-dependent relaxation induced by acetylcholine and the vasoactive prostanoids production of thoracic aorta were evaluated in vitro. Results:Rings from cholesterol group showed significantly decreased endothelium-dependent relaxation compared with that from control group and aspirin group.Treatment with SQ 29548 improved the impaired endothelium-dependent relaxation.Radioimmunoassay measurements showed a significant increase in acetylcholine-stimulated release of thromboxane B 2(TXB 2)in aortae with,but not without endothelium from cholestrerol group,but not that from control group.The release of 6-keto-prostaglandin F 1α (PGF 1a )was not significantly different between control and cholesterol group.Treatment with aspirin(10*!mg/d)caused a significant decrease in the basal release of TXB 2 and 6-keto-PGF 1α from aorta with,but not without endothelium. Conclusions:①The impaired vascular endothelium-dependent relaxation induced by hypercholesterolemia is related to the increasing endothelial production of TXA 2.②Small dosage of aspirin can improve the impaired vascular endothelium-dependent relaxation induced by hypercholesterolemia.