缺氧诱导HIF-1α在子宫内膜异位症巨噬细胞极化异常的作用及机制研究  

Hypoxia regulates the polarization of macrophages through HIF-1αin patients withendometriosis

作　　者：杨如玉 梁炎春[1] 韦雅婧 黄碧淇 杨帆[1] 谭灏[1] 温磊 陆曦 牛刚[1] YANG Ruyu;LIANG Yanchun;WEI Yajing;HUANG Biqi;YANG Fan;TAN Hao;WEN Lei;LU Xi;NIU Gang(Department of Obstetrics and Gynecology,First Affiliated Hospital of Sun Yat-Sen University,Guangzhou 510080,China;不详)

机构地区：[1]中山大学附属第一医院妇产科,广州510080 [2]中山大学中山医学院,广州510089

出　　处：《实用医学杂志》2022年第8期964-969,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:82071618);广东省科技创新战略专项资金(省基础与应用基础研究基金自然科学基金)(编号:2021A1515012615);2021年广东大学生科技创新培育专项资金项目(编号:pdjh2020b0015);2021年和2022年中山大学大学生创新训练计划项目(编号:202110558079,202210698);2021年中山大学附属第一医院柯麟新星人才计划(编号:R08013);广东省医学科研基金项目(编号:B2022069)。

摘　　要：目的探讨缺氧调控HIF-1α对子宫内膜异位症中巨噬细胞极化状态的影响及作用机制。方法收取2021年1月至2021年12月期间的子宫内膜异位症患者的异位病灶(内异症组,n=17)和非子宫内膜异位症患者的正常子宫内膜(对照组,n=20),通过双重免疫荧光实验检测异位病灶和正常子宫内膜中巨噬细胞的分布情况,采用免疫组化检测异位病灶的缺氧情况。缺氧处理THP-1细胞,采用RT-qPCR检测缺氧诱导因子(Hypoxia inducible factor-1α,HIF-1α)的表达和巨噬细胞两种型别特异性标志物的表达。结果子宫内膜异位症异位病灶中巨噬细胞密度高于正常子宫内膜,M1、M2型巨噬细胞密度增加,以M2型为主(P<0.05);异位病灶中的缺氧程度高于正常在位子宫内膜(P<0.05);缺氧可上调HIF-1α诱导巨噬细胞转化为M2型巨噬细胞(P<0.05)。结论缺氧可通过上调HIF-1α调控子宫内膜异位症巨噬细胞极化异常。Objective To explore the effect and mechanism of hypoxia in regulating macrophage polarization through upregulating hypoxia inducible factor-1α(HIF-1α)in endometriosis.Methods The ectopic endometriotic lesions of patients with endometriosis(endometriosis group,n=17)and normal endometrium of patients without endometriosis(control group,n=20)from January 2021 to December 2021 were collected.The distributions of macrophages in ectopic lesions and normal endometrium were detected by double immunofluorescence,and the hypoxic conditions were detected by immunohistochemistry.After treated with hypoxia,we detected the level of HIF-1αand the expression of specific markers of M1 and M2 macrophages by RT-qPCR in THP-1 cells.Results The density of macrophages in ectopic lesions of endometriosis was higher than that of normal endometrium.The density of both M1 and M2 macrophages are increased in endometriosis,but M2 macrophages are the mainly type macrophages in the lesions(P<0.05).The degree of hypoxia in ectopic lesions was higher than that of normal eutopic endometrium(P<0.05).Hypoxia could induce macrophages to transform into M2 macrophages through upregulating HIF-1α(P<0.05).Conclusions Hypoxia regulates the polarization of macrophages in endometriosis through upregulating HIF-1α.

关 键 词：子宫内膜异位症 巨噬细胞极化 缺氧 HIF-1Α 

分 类 号：R711.71[医药卫生—妇产科学]