卡托普利对对氧磷所致血管内皮损伤的保护作用及机制探讨  

Protective effect of captopril on paraoxon-induced vascular endothelial cell injury and its potential mechanism

作　　者：李鹏[1] 吴树金[1] 黄宁江[1] 刘立英[1] 

机构地区：[1]中南大学药学院,长沙410078

出　　处：《中南药学》2007年第5期410-416,共7页Central South Pharmacy

基　　金：国家自然科学基金资助项目(30570754);有机磷酸酯类杀虫剂致动脉粥样硬化及机制研究

摘　　要：目的探讨卡托普利对对氧磷(paraoxon)所致血管内皮功能损伤的保护作用及其机制。方法用大鼠离体血管环和培养的人脐静脉内皮细胞(HUVEC)为实验模型,以血管内皮依赖性舒张(EDR)反应、HUVEC的通透性、内皮细胞活力、内皮细胞的形态学改变及生化参数为指标,用对氧磷作为损伤因子,用血管紧张素转化酶抑制剂(ACEI)卡托普利(captopril)作为保护药,观察了对氧磷对内皮的损伤作用及卡托普利的保护作用。用非巯基类ACEI(依那普利拉,enalaprilat)和抗氧化酶为对照,探讨了卡托普利对对氧磷所致血管内皮损伤的保护作用的机制。结果对氧磷(3.63μmol.L-1)与血管环或内皮细胞共孵30 min,显著性地抑制了血管EDR反应和增加了单层内皮细胞的通透性。卡托普利与血管环共孵30 min,剂量依赖性(0.1、1.0、10μmol.L-1)地显减轻了对氧磷(3.63μmol.L-1)对血管EDR的抑制作用、保护了培养的HUVEC中NO的释放。对氧磷和卡托普利对硝普钠(SNP)诱导的非内皮依赖性舒张反应没有影响。卡托普利(10μmol.L-1)显著性地阻滞了对氧磷所致的单层HU-VEC通透性的增加以及内皮细胞活力的降低、保护了超氧化物歧化酶(SOD)活性、阻滞了丙二醛(MDA)浓度的升高。超氧化物歧化酶、过氧化物酶(catalase)有与卡托普利相似的抗对氧磷损伤作用,但依那普利拉对对氧磷所致损伤无明显保护作用,巯基抑制剂(4-羟基汞苯甲酸普罗比妥钠,cystain)能显著性拮抗卡托普利的保护作用。结论对氧磷能直接损伤血管内皮细胞,卡托普利对氧磷所致的血管内皮细胞损伤有显著性保护作用,其机制可能主要依赖于其所含的巯基的抗氧化作用,而非依赖于抑制血管紧张素转化酶。Objective To explore the protective effect of captopril on the vascular endothelial cells impaired by paraoxon and the potential mechanism. Methods The thoracic aorta rings of rats and cultured human umbilical vein endothelial cells （HUVEC） were exposed to medium containing enalaprilat or antioxidant agents. The endothelial-dependent and non-dependent relaxation of aortic rings in the rats and endothelial cells in HUVEC were assessed by fluid filtration coefficient （Kf） and filtration volume （Jv） to protein in the medium of cultured HUVEC, and the energy and morphological change of endothelial cells and the biochemical indexes were measured. Results Captopril dose-dependently （0. 1, 1, or 10 μmol· L^-1 ） lessened the inhibition of ACh-induced endothelium dependent relaxation （EDR） induced by paraoxon, but did not affect the sodium nitroprusside-induced endothelium-independent relaxation of the aortic rings. Captopril （10 μmol · L^-1） obviously prevented the increase of values of KF and Jv in the endothelial cell monolayer and the decrease of cell energy induced by paraoxon. Simultaneously captopril （10 μmol · L^-1） inhibited the increase of the MDA content and the reduction of both SOD activity and NO content induced by paraoxon in the medium of cultured HUVEC. These effects of Captopril could be inhibited by cystatin, a sulfhydryl group blocking agent. Conclusion Sulfhydryl （SH） -containing ACE inhibitors may protect the endothelial cell from being damaged by paraoxon and the effect of ACE inhibitors may be related to nonenzymatic antioxidant defenses.

关 键 词：卡托普利 对氧磷 内皮细胞 离体血管舒张反应 内皮细胞通透性 人脐静脉内皮细胞 大鼠 

分 类 号：R965[医药卫生—药理学]