醛固酮诱导的氧化应激损伤内皮祖细胞介导的血管内皮修复功能  

Aldosterone-induced Oxidative Stress Impairs Endothelial Progenitor Cells-mediated Endothelial Repair Function

作　　者：丁美琳[1] 徐敏[2] 吴芳[1] 李晨[1] 李进[1] 陈龙[1] DING Mei-lin;XU Min;WU Fang;LI Chen;LI Jin;CHEN Long(Department of Geriatric,The First Affiliated Hospital,Sun Yat-Sen University,Guangzhou 510080,China;Department of Obstetrics and Gynecology,The First Affiliated Hospital,Sun Yat-Sen University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第一医院老年病科,广东广州510080 [2]中山大学附属第一医院妇产科,广东广州510080

出　　处：《中山大学学报（医学版）》2018年第6期818-826,共9页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81100201);广东省自然科学基金(2017A030313823);广东省医学科学技术研究基金(C2015047)

摘　　要：【目的】进一步探索醛固酮对循环中内皮祖细胞(EPC)功能的影响及其分子机制有待。【方法】抽取健康志愿者外周血分离培养EPC,研究浓度梯度醛固酮干预(0,10,100,1000 nmol/L)对EPC体外迁移、黏附功能的影响。建立裸鼠颈动脉内皮拉脱损伤模型,在体研究醛固酮干预对EPC介导的血管内皮修复作用的影响。应用二氯二氢荧光素二醋酸酯(DCF)荧光探针研究醛固酮干预对EPC内活性氧簇(ROS)生成的影响。分别采用盐皮质激素受体(MR)拮抗剂—螺内酯、NADPH氧化酶阻断剂—夹竹桃麻素阻断EPC的MR和NADPH氧化酶,研究醛固酮诱导氧化应激损伤EPC血管内皮修复功能的分子信号通路。【结果】醛固酮干预明显抑制EPC体外迁移、黏附功能,损伤其介导的在体血管内皮修复能力。醛固酮干预导致EPC的ROS生成明显升高。螺内酯、夹竹桃麻素干预可以减少醛固酮诱导的ROS生成,并且可以对抗醛固酮损伤EPC功能。【结论】醛固酮通过MR激活NADPH氧化酶诱导氧化应激损伤EPC介导的血管内皮修复功能。【Objective】To determine the effect and molecular mechanisms of aldosterone on the endothelial repair capacity of endothelial progenitor cells(EPC)in peripheral blood.【Method】EPC were cultured from peripheral blood mononuclear cells of healthy subjects.In vitro EPC function was assayed by migration and adhesion after treatment with different concentration of aldosterone(0,10,100,1000 nmol/L).In vivo endothelial repair capacity of EPC was evaluated by transplantation into a nude mouse carotid endothelial denudation model.The reactive oxygen species(ROS)was detected by 2’,7’-dichlorodihydrofluorescein diacetate(DCF)-fluorescent probe under fluorescence microscopy.【Result】Both the in vitro function and in vivo endothelial repair capacity of EPC were impaired obviously by aldosterone treatment.ROS production was distinctly increased after aldosterone treatment as well.Co-treatment with mineralocorticoid receptor inhibitor spironolactone or NADPH oxidase blocker apocynin prevented aldosterone-induced ROS production and recovered aldosterone-impaired EPC function.【Conclusion】Aldosterone-induced oxidative stress impairs endothelial repair capacity of EPC via MR-dependent activation of NADPH oxidase.

关 键 词：血管内皮 内皮祖细胞 醛固酮 氧化应激 NADPH氧化酶 

分 类 号：R543.5[医药卫生—心血管疾病]