摘要
目的 探讨复发性流产(RSA)患者绒毛组织中基质金属蛋白酶(MMPs)的调控机制。 方法 选取2016年2—5月期间就诊于苏州大学附属第一医院妇产科计划生育门诊的RSA患者24例为RSA组,同期健康早孕流产患者26例为对照组,酶联免疫吸附法(ELISA)检测血浆肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β水平,逆转录-聚合酶链式反应(RT-PCR)检测患者绒毛组织中TNF-α、IL-1β、核转录因子(NF)-κB、核转录因子抑制蛋白(IκB)β、MMP-9和MMP-2的mRNA表达情况,采用蛋白印迹法检测分析NF-κB、IκBβ、MMP-9、MMP-2的蛋白表达。 结果 ①RSA组血浆中TNF-α水平为(2.84±0.62) μg/L,显著高于对照组的(1.32±0.43) μg/L (P=0.047)。②RSA组绒毛组织中TNF-α、NF-κB1、RelA、MMP-9 mRNA相对表达量均高于对照组,差异均有统计学意义(P<0.001、P<0.001、P=0.003、P<0.001),IkBβ mRNA表达量显著低于对照组(P=0.011);③ RSA组绒毛组织中MMP-9、NF-κB p65和p50的蛋白表达水平均高于对照组,差异均有统计学意义(P=0.001、P=0.001、P<0.001),IκBβ的蛋白表达水平显著低于对照组(P<0.001)。 结论 外周血中TNF-α水平的升高,可影响绒毛组织中IκB蛋白的降解,活化NF-κB使其表达水平升高,进一步导致MMP-9表达升高,从而引起蜕膜细胞外基质过度降解导致胚胎脱落,最终导致流产发生。
Objective To investigate the expression of matrix metalloproteinas (MMPs) in villi of patients with recurrent spontaneous abortion (RSA), and analyze the relationship and clinical significance between MMPs and RSA. Methods During February to May 2016 at Obstetrics and Gynecology, the First Affiliated Hospital of Soochow University, 24 patients with RSA were selected as RSA group, 26 healthy pregnant women in the same period were selected as control group, tumor necrosis factor (TNF)-α, interleukin (IL)-1β levels in plasma were measured by enzyme linked immunosorbent assay (ELISA). IL-1β, nuclear factor (NF)-κB, inhibitor of tumor necrosis factor(IκB)β, MMP-9 and MMP-2 were detected by RT-PCR, and the protein expression of MMP-9, MMP-2, NF-κB and IκBβ were detected by Western blotting. Results 1) The level of TNF-α in plasma of RSA group [(2.84±0.62) μg/L] was higher than that in control group [(1.32±0.43) μg/L] (P=0.047). 2) The expressions of TNF-α, NF-κB1, RelA and MMP-9 mRNA in villi of RSA group were significantly higher than those in control group (P<0.001, P<0.001, P=0.003, P<0.001), and the expression of IκBβ mRNA was significantly lower than that of control group (P=0.011). 3) The levels of MMP-9, NF-κB p65 and p50 protein in villi were significantly higher than those in control group (P=0.001, P=0.001, P<0.001), and the level of IκBβ protein in villi was significantly lower than that in control group (P<0.001). Conclusion The increase of TNF-α level in peripheral cells can affect the degradation of the protein of IκB in villi. The elevated expression of NF-κB increases the level of MMP-9, the excessive degradation of extracellular matrix in decidual leads to the shedding of embryo, and may induce miscarriage eventually.
作者
施林领
伯乐
李海燕
黄慧妙
奚星澍
滕云
茅彩萍
Shi Linling;Bo Le;Li Haiyan;Huang Huimiao;Xi Xingshu;Teng Yun;Mao Caiping(Obstetrics and Gynecology,the First Affiliated Hospital of Soochow University,Suzhou 215006,China;Reproductive Medicine Center,the First Affiliated Hospital of Soochow University,Suzhou 215006,China)
出处
《中华生殖与避孕杂志》
CAS
CSCD
北大核心
2019年第1期17-21,共5页
Chinese Journal of Reproduction and Contraception
基金
江苏省社会发展项目(BE20156)
江苏省妇幼健康“生殖医学”重点学科项目(FXK201749)
江苏省“科教强卫”医学重点人才项目(ZDRCA2016044)
苏州市“科教兴卫”青年科技项目(KJXW2016007).
关键词
自然流产
绒毛组织
基质金属蛋白酶
复发性流产
Spontaneous abortion
Chorionic villi
Matrix metalloproteinases
Recurrent spontaneous abortion
作者简介
通信作者:茅彩萍,Email:maocp1018@163.com,电话:+86-512-67780720.
