宫内母源性糖皮质激素编程子代肝脏发育及相关疾病易感  

Intrauterine maternal glucocorticoid programs the offspring's liver development and related disease susceptibility

作　　者：陈凯琪 刘可欣 汪晖[1,2] CHEN Kai-Qi;LIU Ke-Xin;WANG Hui(Department of Pharmacology,Wuhan University School of Basic Medical Sciences,Wuhan 430071,China;Hubei Provincial Key Laboratory of Developmentally Originated Disease,Wuhan 430071,China)

机构地区：[1]武汉大学基础医学院药理学系,武汉430071 [2]湖北省发育源性疾病重点实验室,武汉430071

出　　处：《生命科学》2023年第9期1136-1146,共11页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金重点项目(82030111)。

摘　　要：胎血基础糖皮质激素(glucocorticoid, GC)主要来自母体,其水平是决定胎儿多器官发育及功能成熟的关键。然而,孕期母体受内、外环境刺激后,其内源性GC水平或胎盘GC屏障功能会发生改变,进而引起宫内母源性GC水平异常。大量研究发现,宫血GC水平过高或过低均可导致子代肝脏发育及功能异常,导致出生后相关疾病易感,这主要与GC调控的信号通路、转录因子及表观遗传修饰的改变有关。迄今,宫内母源性GC水平对子代肝脏发育的影响及其编程机制尚未系统阐明。本文结合最新流行病学和实验研究,综述了宫内时期肝脏的生理发育过程及内源性GC的调控作用,重点介绍宫内母源性GC水平改变对子代肝脏发育及相关疾病易感性的影响,并阐明其网络调控机制,这对于解析肝脏生理发育与病理改变并探究相关疾病易感的宫内起源机制具有重要意义。Fetal blood glucocorticoid(GC)mainly comes from the mother,and GC level is the key to fetal organ development and functional maturation.However,when prenatally exposed to adverse internal and external environments,the maternal endogenous GC level or the function of placental GC barrier will be changed,thus leading to an abnormal intrauterine GC level,which will cause abnormal development and function in offspring liver,and even predisposition to related diseases after birth.These are found mainly related to signaling pathway,transcription factors and epigenetic modifications regulated by GC.Until now,the effects of maternal GC in utero on offspring liver development and the programming mechanisms have yet to be systematically elucidated.Based on the latest epidemiological and experimental studies,this paper reviewed the physiological development of intrauterine liver and the regulatory mechanism of endogenous GC,focusing on the effects of intrauterine maternal GC level changes on offspring liver development and susceptibility to related diseases,and the regulatory network,which is of great significance to analyze the liver's physiological development and pathological changes and explore the intrauterine origins of the susceptibility of related diseases.

关 键 词：糖皮质激素 肝脏发育 疾病易感 宫内编程机制 表观遗传修饰 

分 类 号：Q132.4[生物学—普通生物学] R575[医药卫生—消化系统]