对氧磷对血管内皮细胞的损伤作用及机制探讨  

Paraoxon-Induced Injuries of Vascular Endothelial Cell and Exploration of Potential Mechanisms

作　　者：李鹏[1] 刘立英[1] 周寿红[1] 吴树金[1] 

机构地区：[1]中南大学药学院

出　　处：《中国动脉硬化杂志》2007年第9期666-670,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(30570754)

摘　　要：目的为探讨有机磷酸酯对血管内皮细胞和血管内皮功能是否有直接的损伤作用。方法用不同浓度的对氧磷分别与大鼠离体血管环和培养的人脐静脉单层内皮细胞共孵不同的时间,以乙酰胆碱引起的血管内皮依赖性舒张反应和单层内皮细胞通透性等为观察指标,检测对氧磷对血管内皮的损伤作用。结果对氧磷(36.3nmol/L^36.3μmol/L)与血管环共孵,呈浓度和时间依赖性地显著抑制乙酰胆碱诱导的内皮依赖性舒张反应,而对硝普钠引起的非内皮依赖性舒张反应没有明显的影响。对氧磷与内皮细胞共孵不同的时间,呈浓度和时间依赖性地显著增加单层内皮细胞的通透性。对氧磷在损伤血管内皮的同时也导致了血管组织及细胞培养液中一氧化氮浓度和超氧化物歧化酶活性的降低、脂质过氧化代谢产物丙二醛浓度的升高。加入左旋精氨酸能部分拮抗对氧磷对血管内皮功能的损伤作用,用阿托品预处理则不影响对氧磷的作用。结论该研究提示对氧磷对血管内皮细胞有直接损伤作用,其机制可能与对氧磷诱发氧化应激,进而导致脂质过氧化反应发生和增加内皮细胞的通透性有关。Aim To explore whether paraoxon, an active component of organophosphate, can directly injure vascular endothelial cells in vitro and to explore the potential mechanisms. Method The thorac aortic rings of healthy sprague-dawley rats and cultured human umbilical vein endothelial cells （hUVEC） were exposed to medium contained different concentrations （36.3 nmol/L- 36.3 μmol/L） of paraoxon and co-inoubation different time. Both endothelial-dependent and non-dependent relaxation of aortie rings in rats and endothelial monolayer permeability in acetylcholine （ Ach）-induced endothelium dependent relaxation （EDR） and increased hUVEC was assayed. Results Paraoxon concentration and time-dependently inhibited permeability of the endothelial monolayer in hUVEC. Paraoxon also simultaneously resulted in a reduction of both superoxide dismutase （SOD） activity and nitric oxide （NO） content and an increase of malondialdehyde （MDA） content in both aortic tissues and cultured cellular medium. But sodium nitroprusside-indueed endothelium-independent relaxation of aortic rings were not affected by paraoxon. The injurious effects of paraoxon to EDR was partly lessened by added L-arginine, but not done by pretreatment of atropine. ConcluSion Paraoxon could directly injure vascular endothelium cells and EDR. The mechanisms of endothelial dysfunction induced by paraoxon may relate to trigger oxidative stress and formation of lipid peroxidafion by oxidation-stress, and the increase of endothelial cell monolayer permeability.

关 键 词：病理学与病理生理学 对氧磷 离体血管环 内皮依赖性舒张反应 内皮细胞 内皮细胞通透性 

分 类 号：R363[医药卫生—病理学]