肾素-血管紧张素系统在胎儿宫内生长迟缓发生中的作用机制及防治靶标研究进展  

Research progress in mechanisms and prevention targets of renin angiotensin system in intrauterine growth restriction

作　　者：张皓南 肖浩[1,3] 陈雅文 敖英 汪晖[2,3] ZHANG Hao-nan;XIAO Hao;CHEN Ya-wen;AO Ying;WANG Hui(Department of Joint and Sports Medicine,Zhongnan Hospital,Wuhan University,Wuhan 430071,China;Department of Pharmacology,School of Basic Medical Sciences,Wuhan University,Wuhan 430071,China;Hubei Provincial Key Laboratory of Developmentally Originated Disease,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院关节与运动医学科,湖北武汉430071 [2]武汉大学基础医学院药理学系,湖北武汉430071 [3]发育源性疾病湖北省重点实验室,湖北武汉430071

出　　处：《中国药理学与毒理学杂志》2023年第3期207-216,共10页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(82104301)。

摘　　要：成人疾病具有胎儿起源,且与孕期不良环境导致的胎儿宫内生长迟缓(IUGR)有关。肾素-血管紧张素系统(RAS)作为机体重要的内分泌系统,在胎儿多器官发育及其功能稳态调节中起着至关重要的作用。研究发现,IUGR胎儿的多器官局部RAS功能存在明显改变。结合国内外最新临床和动物研究进展,本文综述RAS功能异常介导IUGR胎儿多器官(如胎盘、肾、心血管和骨)发育不良,阐明IUGR胎儿多器官RAS成分改变的表观遗传调控机制包括DNA甲基化、组蛋白修饰和非编码RNA等,并提出血管紧张素转换酶、血管紧张素Ⅱ受体为IUGR胎儿成年后疾病易感的早期防治靶标。本综述为阐明多器官局部RAS功能改变在IUGR发生中的重要作用及揭示IUGR相关胎源性疾病的早期防治靶标提供了理论和实验依据。Adult diseases are fetal of origin and related to fetal intrauterine growth restriction(IUGR)caused by adverse environments during pregnancy.As an important endocrine system,the renin angiotensin system(RAS)plays a vital role in fetal multiple-organ development and functional homeostasis regulation.It has been found that the local RAS function of multiple organs in the IUGR fetus has been significantly changed,but its mechanism and prevention targets have not been systematically reviewed.Combined with the latest clinical and animal research progress at home and abroad,this reviewed outlines how RAS dysfunction mediates multiple organ dysplasia(such as placenta,kidney,cardiovascular,bone)in the IUGR fetus,elucidateds the epigenetic regulation mechanism of RAS composition changes in multiple organs of the IUGR fetus(such as DNA methylation,histone modification,non-coding RNA),and proposes angiotensin-converting enzyme and angiotensinⅡreceptors as early prevention targets for disease susceptibility of the IUGR fetus in adulthood.This article is expected to help clarify the important role of local RAS function changes in multiple organs in the occurrence of IUGR and reveal the early prevention and treatment targets of fetal diseases in IUGR.

关 键 词：肾素-血管紧张素系统 宫内生长迟缓 胎儿 发育毒性 

分 类 号：R394.1[医药卫生—医学遗传学]