2019 年第 7 期 第 14 卷

人β防御素2在合并绒毛膜羊膜炎的未足月胎膜早破患者胎盘胎膜组织中的表达

Expression of human β-defensin-2 in placenta and fetal membranes in patients with premature rupture of membranes complicated with chorioamnionitis

作者：王颖

英文作者：

单位：037003山西医科大学附属大同煤矿集团有限责任公司总医院产科

英文单位：

关键词：未足月胎膜早破；绒毛膜羊膜炎；人β防御素2；Toll样受体4/核因子κB通路

英文关键词：

• 摘要：

• 【摘要】目的    观察人β防御素2（HBD-2）在合并绒毛膜羊膜炎的未足月胎膜早破患者胎盘胎膜组织中的表达。方法    选取2016年6月至2018年3月山西医科大学附属大同煤矿集团有限责任公司总医院收治的未足月胎膜早破孕妇61例为观察组，根据是否合并绒毛膜羊膜炎将观察组孕妇进一步分为绒毛膜羊膜炎组（23例）、非绒毛膜羊膜炎组（38例），另取同期收治的除胎膜早破以外其他因素引发早产而终止妊娠，且胎盘病理组织检查排除绒毛膜羊膜炎的孕妇61例为对照组。收集胎膜破口处的胎膜组织，以及距离最近的胎盘组织。实时荧光定量聚合酶链反应和蛋白质印迹法检测HBD-2、Toll样受体4（TLR-4）、核因子κB（NF-κB）p65 mRNA和蛋白表达水平。比较胎盘、胎膜组织中的HBD-2、TLR-4、NF-κB p65 mRNA和蛋白表达水平。结果    观察组胎盘、胎膜组织中HBD-2、TLR-4、NF-κB p65 mRNA和蛋白相对表达量明显高于对照组［胎盘组织中mRNA：（26.0±3.8）比（11.8±1.2）、（16.2±3.6）比（6.1±1.5）、（31.5±9.6）比（19.7±6.2），蛋白：（13.2±2.2）比（5.2±0.8）、（15.8±2.6）比（7.7±1.9）、（10.0±1.8）比（3.1±0.5）；胎膜组织中mRNA：（24.1±2.2）比（12.4±1.5）、（17.4±2.3）比（5.8±1.6）、（28.2±8.1）比（16.5±7.3），蛋白：（11.6±1.8）比（2.2±0.5）、（9.2±1.5）比（2.5±0.6）、（10.7±2.6）比（4.2±1.8）］，差异均有统计学意义（P<0.01或P<0.05）。绒毛膜羊膜炎组胎盘、胎膜组织中HBD-2、TLR-4、NF-κB p65 mRNA和蛋白相对表达量明显均高于非绒毛膜羊膜炎组，差异均有统计学意义（P<0.01或P<0.05）。Pearson分析结果显示，绒毛膜羊膜炎组胎盘、胎膜组织中TLR-4表达与NF-κB p65、HBD-2呈正相关，NF-κB p65表达与HBD-2呈正相关（均P<0.01）。非绒毛膜羊膜炎组胎盘、胎膜组织中NF-κB p65表达与HBD-2呈正相关（P<0.01），TLR-4表达与NF-κB p65和HBD-2均无相关性（均P>0.05）。结论    合并绒毛膜羊膜炎的未足月胎膜早破患者胎盘和胎膜组织中存在HBD-2高表达；其发病机制可能与激活TLR-4/NF-κB信号通路，上调HBD-2 表达，启动机体强烈的免疫应答有关。

• 【Abstract】Objective    To analyze the expression of human β-defensin-2(HBD-2) in placenta and fetal membranes in patients with premature rupture of membranes complicated with chorioamnionitis. Methods    From June 2016 to March 2018, 61 pregnant women with preterm premature rupture of membranes admitted to With The Coal Group General Hospital, Shanxi Medical University were enrolled as observation group, including 23 cases of chorioamnionitis（chorioamnionitis group） and 38 cases in non-chorioamnionitis group; 61 pregnant women with premature delivery without chorioamnionitis were enrolled as control group. Fetal membrane tissue of the rupture and placenta tissue nearest to the rupture were sampled. Expressions of HBD-2, Toll-like receptor-4(TLR-4), nuclear factor-κB(NF-κB) p65 were detected by real-time quantitative polymerase chain reaction and Western boltting. Results    Relative expression levels of HBD-2, TLR-4 and NF-κB p65 mRNA and protein in placenta and fetal membranes in observation group were significantly higher than those in control group［placenta mRNA: （26.0±3.8） vs （11.8±1.2）, （16.2±3.6） vs （6.1±1.5）, （31.5±9.6） vs （19.7±6.2）; placenta protein: （13.2±2.2） vs （5.2±0.8）, （15.8±2.6） vs （7.7±1.9）, （10.0±1.8） vs （3.1±0.5）； fetal membranes mRNA: （24.1±2.2） vs （12.4±1.5）, （17.4±2.3） vs （5.8±1.6）, （28.2±8.1） vs （16.5±7.3）; fetal membranes protein: （11.6±1.8） vs （2.2±0.5）, （9.2±1.5） vs （2.5±0.6）, （10.7±2.6） vs （4.2±1.8）］(P<0.01 or P<0.05). Relative expression levels of HBD-2, TLR-4 and NF-κB p65 mRNA and protein in placenta and fetal membranes in chorioamnionitis group were significantly higher than those in non-chorioamnionitis group(P<0.01 or P<0.05). Pearson analysis showed that the expression of TLR-4 in placenta and fetal membranes in chorioamnionitis group was positively correlated with NF-κB p65 and HBD-2; the expression of NF-κB p65 was positively correlated with HBD-2(all P<0.01). In non-chorioamnionitis group, the expression of NF-κB p65 in placenta and fetal membranes was positively correlated with HBD-2(P<0.01); TLR-4 expression showed no correlation with NF-κB p65 and HBD-2(both P>0.05). Conclusion    HBD-2 is highly expressed in placenta and fetal membranes in patients with premature rupture of membranes complicated with chorioamnionitis; the pathogenesis may be related to the activation of strong immune response through TLR-4/NF-κB signaling pathway and up-regulation of HBD-2.