胎膜组织人β防御素2、核因子KB p65、Toll样受体-4表达与未足月胎膜早破孕妇绒毛膜羊膜炎发生的关系

Relationship between human β defensin 2, nuclear factor KB p65 and Toll-like receptor-4 in fetal membrane tissues and the occurrence of chorioamnionitis in full-term pregnant women with preterm premature rupture of membranes

目的 探讨胎膜组织人β防御素2(HBD-2)、核因子κB p65(NF-κB p65)、Toll样受体-4(TLR-4)表达与未足月胎膜早破(PPROM)孕妇绒毛膜羊膜炎发生的关系。方法 选取铜仁市人民医院2019年5月-2020年12月106例PPROM孕妇,根据分娩时胎膜组织病理结果分为绒毛膜羊膜炎组(n=51)、非绒毛膜羊膜炎组(n=55),并将绒毛膜羊膜炎组按照炎症程度分为轻度炎症组(n=16)、中度炎症组(n=18)、重度炎症组(n=17)三个亚组,观察不同组别胎膜组织HBD-2、NF-κB p56、TLR-4 mRNA表达水平,通过绘制受试者工作曲线(ROC)评价三项指标对疾病的诊断评估价值,分析PPROM孕妇发生绒毛膜羊膜炎的危险因素。结果 绒毛膜羊膜炎组胎膜组织HBD-2、NF-κB p56、TLR-4 mRNA表达水平高于非绒毛膜羊膜炎组(P<0.05);胎膜组织HBD-2、NF-κB p56、TLR-4 mRNA表达水平联合检测评估PPROM合并绒毛膜羊膜炎ROC曲线下面积为0.906,高于各项指标单独检测ROC曲线面积0.787、0.818、0.759(P<0.05);Logistic回归分析显示妊娠期肥胖、合并阴道炎症、合并妊娠期糖尿病、HBD-2 mRNA高表达、NF-κB p56 mRNA高表达、TLR-4 mRNA高表达是PPROM孕妇发生绒毛膜羊膜炎的影响因素(P<0.05)。结论 PPROM合并绒毛膜羊膜炎孕妇胎膜组织HBD-2、NF-κB p56、TLR-4表达水平升高,其升高趋势是PPROM合并绒毛膜羊膜炎发生的影响因素,三者结合可作为疾病诊断的生物标志物。

OBJECTIVE To explore the relationship between human β-defensin 2(HBD-2), nuclear factor κB p65(NF-κB p65) and Toll-like receptor-4(TLR-4) in fetal membrane tissues and the occurrence of chorioamnionitis in full-term pregnant women with preterm premature rupture of membranes(PPROM). METHODS A total of 106 pregnant women with PPROM in Tongren People′s Hospital between May 2019 and Dec 2020 were enrolled. They were divided into the chorioamnionitis group(n=51) and non-chorioamnionitis group(n=55) according to pathological test of fetal membranes tissues at delivery, and patients in the chorioamnionitis group were further divided into subgroups including the mild group(n=16), moderate group(n=18) and severe group(n=17) by the inflammation degrees. The mRNA expression levels of HBD-2, NF-κB p56 and TLR-4 in the fetal membrane tissues of all groups were observed. The diagnostic value of the three indexes for disease diagnosis was assessed by ROC curves. The risk factors for chorioamnionitis in PPROM pregnant women were analyzed. The relationship between HBD-2, NF-κB p56, TLR-4 mRNA levels and inflammation degrees was explored. RESULTS The mRNA expression levels of HBD-2, NF-κB p56 and TLR-4 in the chorioamnionitis group were significantly higher than those in the non-chorioamnionitis group(P<0.05). The value of area under the ROC curve(AUC) of the combined detection of HBD-2, NF-κB p56 and TLR-4 mRNA levels for the diagnosis of PPROM was 0.906, which was significantly higher than that of the three indexes individually(0.787, 0.818, 0.759)(P<0.05). Multivariate Logisitic regression analysis showed that gestational obesity, vaginal inflammation, gestational diabetes, high expressions of HBD-2, NF-κB p56 and TLR-4 mRNA were independent risk factors for chorioamnionitis in PPROM pregnant women(P<0.05). CONCLUSION The expression levels of HBD-2, NF-κB p56 and TLR-4 in fetal membrane tissues increase in pregnant women with PPROM and chorioamnionitis. And their higher expression are independent risk factors for PPROM combined with chorioamnionitis. The combination of the three indexes can be applied as a biomarker for disease diagnosis.