子痫前期孕妇母胎界面炎症介质的表达与线粒体自噬的相关性研究

Study of the Correlation between Expression of Inflammatory Mediators at Maternal-Fetal Interface and Mitophagy in Pre-Eclampsia Pregnant Women

目的:探讨子痫前期(PE)孕妇母胎界面炎症介质的表达量以及线粒体自噬的发生情况,并探究两者的相关性。方法:选取2018年6月-2019年2月于南方医科大学附属深圳妇幼保健院住院的35例正常孕妇(对照组)、33例轻度PE孕妇(轻度PE组)及37例重度PE(重度PE组)。检测胎盘剥离面血清IL-1β、IL-18、TNF-α的表达量,分析母胎界面炎症形态学变化,观察胎盘滋养细胞线粒体发生情况,检测自噬相关分子BNIP3及DRAM1 mRNA及蛋白的表达变化,并进行炎症介质与线粒体自噬的相关性分析。结果:PE孕妇胎盘剥离面血清IL-1β、IL-18、TNF-α表达量显著高于对照组(P<0.01),重度PE组表达量明显高于轻度PE组(P<0.01)。HE染色显示PE孕妇胎盘组织炎症细胞浸润程度高于对照组。透射电镜可见重度PE组孕妇胎盘滋养细胞线粒体自噬阳性率为(2.61±1.07)%,轻度PE组为(7.65±3.19)%,均明显低于对照组[(14.07±3.11)%,P<0.01]。PE孕妇BNIP3及DRAM1 mRNA及蛋白表达均低于对照组(P<0.01)。相关性分析表明PE孕妇IL-1β、IL-18、TNF-α等炎症介质的表达量与线粒体自噬阳性率呈负相关。结论:PE孕妇滋养细胞线粒体自噬活性下降,受损线粒体积累可能导致母胎界面IL-1β、IL-18、TNF-α等炎症介质升高,从而参与PE发病。

Objective:To investigate the expression of IL-1β,IL-18 and TNF-αin maternal-fetal interface of preeclampsia(PE)pregnant women and the occurrence of mitophagy,and to explore the correlation between them.Methods:From June 2018 to February 2019,35 normal pregnant women(control group),33 mild PE pregnant women(mild PE group)and 37 severe PE pregnant women(severe PE group)hospitalized in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University were selected.The expression of IL-1β,IL-18 and TNF-αin serum was detected.The morphological changes of maternal-fetal interface inflammation were analyzed.The occurrence of mitophagy in placental trophoblasts was observed.RT-PCR and Western blotting were used to detect the expression of BNIP3,DRAM1 mRNA and their proteins,and the correlation between inflammatory mediators and mitophagy were analyzed.Results:The expression of IL-1β,IL-18 and TNF-αin serum of pregnant women in PE group was significantly higher than that of normal pregnant women(P<0.01).The expression of IL-1β,IL-18 and TNF-αin severe PE group was significantly higher than that of mild PE group(P<0.01).HE staining showed that the infiltration of inflammatory cells in placenta tissue of PE group was higher than that of control group;Transmission electron microscopy showed that the positive rate of mitophagy in severe PE group was(2.61±1.07)%,in mild PE group was(7.65±3.19)%,which were significantly lower than that in control group[(14.07±3.11)%,P<0.01].RT-PCR and Western blotting showed that the expression of BNIP3 and DRAM1 in PE pregnant women were down-regulated(P<0.01).The correlation analysis showed a negative correlation between the expression of inflammatory mediators such as IL-1α,IL-18,TNF-αand the positive rate of mitophagy.Conclusions:The mitophagy activity of trophoblasts in PE pregnant women decreased,the accumulation of damaged mitochondria may lead to the increase of inflammatory mediators such as IL-1β,IL-18 and TNF-αat the maternal-fetal interface,which may be involved in the pathogenesis of PE.