内皮功能障碍的发生机制  

The pathogenesis of endothelial dysfunction

作　　者：张城林 何蕾 王力 黄聿 ZHANG ChengLin;HE Lei;WANG Li;HUANG Yu(Department of pathophysiology,Shenzhen University Health Science Center,Shenzhen 518061,China;Shenzhen Research Institute,The Chinese University of Hong Kong,Shenzhen 518057,China;Department of Biomedical Sciences,City University of Hong Kong,Hong Kong,China)

机构地区：[1]深圳大学医学部病理生理学系,深圳518061 [2]香港中文大学深圳研究院,深圳518057 [3]香港城市大学生物医学系,中国香港

出　　处：《中国科学：生命科学》2022年第5期691-698,共8页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:91939302,81561128017,82000056);香港研究资助局高级研究学者项目(批准号:2021-4S04);香港研究资助局协作研究计划(批准号:C4024-16W);香港研究资助局一般研究项目(批准号:14112919);香港医疗卫生研究基金(批准号:05161746)资助。

摘　　要：内皮功能障碍是糖尿病、高血压及动脉粥样硬化等多种心血管疾病最常见的病理特征,可发生在主动脉和肾动脉等大血管,亦可累及微血管造成视网膜和肾功能损伤.内皮来源的血管舒张因子(如一氧化氮)合成与分泌减少或血管收缩因子(如血管紧张素Ⅱ、内皮素-1、活性氧和收缩型环氧合酶代谢产物)合成与分泌增多是造成内皮功能障碍的主要原因,可引发高血压、动脉粥样硬化、心肌缺血和心衰等疾病.本文以本课题组前期研究工作为核心,从肾素-血管紧张素、环氧合酶2、骨形态发生蛋白4、氧化应激和炎症反应等方面,就内皮功能障碍的发生机制进行总结,希望能据此找到内皮功能障碍发生发展的关键分子靶标,为糖尿病和高血压相关血管并发症的基础和临床研究提供新的思路.Endothelial dysfunction is the most common pathological feature of diabetes,hypertension and atherosclerosis.Endothelial dysfunction can occur not only in large conduit arteries such as aorta and renal artery,but also in microvascular circulation in the retina and kidney.Decreased production and secretion of endothelium-derived vasodilator factors(mainly nitric oxide)or increased synthesis and release of vasoconstrictor factors(such as angiotensinⅡ,endothelin-1,reactive oxygen species and cyclooxygenase metabolites)are the main causes of endothelial dysfunction,which is closely associated with pathogenesis of hypertension,diabetes,atherosclerosis,myocardial ischemia,and heart failure.This review briefly summarizes the mechanisms underlying endothelial dysfunction in relation to activation of the renin angiotensin system,cyclooxygenase 2,and bone morphogenetic protein 4,as well as increased oxidative stress and inflammatory response in blood vessels,hoping to identify the key molecular mediators of endothelial dysfunction,thereby providing new clues for both basic and translational research in cardio-metabolic biology and medicine.

关 键 词：内皮细胞功能障碍 肾素-血管紧张素系统 环氧合酶-2 骨形态发生蛋白4 炎症反应 血流剪切力 

分 类 号：R54[医药卫生—心血管疾病]