外周血HMGB1、sTLR4 表达与亚临床绒毛膜 羊膜炎相关胎膜早破及早发型败血症的关系

Relationship among HMGB1 and sTLR4 in PROM parturient, HCA associated with PROM and neonatal EOS

摘要:

目的 探讨母体外周血高迁移率族蛋白B1（HMGB1）和可溶性Toll 样受体4（sTLR4）表达 与亚临床绒毛膜羊膜炎（HCA）相关胎膜早破及新生儿早发型败血症（EOS）的关系。方法 收集2017 年 5 月—2018 年4 月在成都市第二人民医院产科足月分娩的胎膜早破（>12 h）产妇314 例。根据分娩后胎盘 病理检查结果，分为HCA 组135 例和非HCA 组179 例；另外根据新生儿随访情况，将受试对象分为EOS 组 21 例和非EOS 组293 例。采集受试对象第一产程静脉血，比较各组产妇外周血HMGB1、sTLR4 水平，并绘 制受试者工作特征（ROC）曲线。结果 HCA 组WBC、HMGB1 及sTLR4 水平高于非HCA 组（P <0.05）。 HMGB1、sTLR4、WBC 联合诊断HCA 的曲线下面积（AUC）为0.864（95% CI ：0.826，0.895），敏感性 和特异性分别为0.686（95% CI ：0.623，0.694）和0.901（95% CI ：0.871，0.925）。经多因素Logistic 回归模 型分析，产妇临产外周血HMGB1[Ol ^ R=5.899（95% CI ：2.413，15.386）] 是发生HCA 的独立危险因素，而 sTLR4[Ol ^ R=0.771（95% CI ：0.624，0.914）] 是发生HCA 的独立保护因素。EOS 组孕妇HMGB1、sTLR4 水平高于非EOS 组，合并HCA 例数多于非EOS 组（P <0.05）。HMGB1、sTLR4 联合预测EOS 的AUC 为 0.888（95% CI ：0.840，0.926），敏感性和特异性分别为0.861（95% CI ：0.837，0.882）和0.768（95% CI ： 0.717，0.804）。结论 母体血清HMGB1 及其受体sTLR4 水平与HCA 及EOS 的发生密切相关，对于HCA 的早期诊断及新生儿EOS 的早期预警都有一定临床意义。

Abstract:

Objective To discuss the relationship among the high-mobility group box-1 (HMGB1), soluble Toll-like receptor 4 (sTLR4) in parturient, histological chorioamnionitis (HCA) associated with premature rupture of membrane (PROM) and early-onset neonatal sepsis (EOS). Methods From May 2017 to April 2018, 314 PROM (>12 h) parturient in our hospital were retrospectively collected and divided into HCA group and non-HCA group according to histological examination of the placenta, or divided into EOS group and non-EOS group according to perinatal outcome. The levels of HMGB1 and sTLR4 in peripheral blood were detected and analyzed by receiver operating characteristic (ROC) curve. Results The levels of WBC, HMGB1 and sTLR4 in HCA parturient (n = 135, 42.99%) were higher than these in parturient (n = 179, 57.01%) without HCA (P < 0.05). The area under the ROC curve (AUC) of combined diagnosis was 0.864 (95% CI: 0.826, 0.895), while the sensitivity and specificity were respectively 0.686 (95% CI: 0.623, 0.694) and 0.901 (95% CI: 0.871, 0.925). According to the results of Logistic multiple stepwise regression analysis, HMGB1 [Ol ^ R = 5.899 (95% CI: 2.413, 15.386)] was the independent risk factor of HCA; and sTLR4 [Ol ^ R = 0.771 (95% CI: 0.624, 0.914)] was an independent protective factor. The levels of HMGB1 and sTLR4 in EOS group (n = 21, 6.69%) were higher than these in non-EOS group (n = 293, 93.31%) (P < 0.05). The AUC of HMGB1 combined with sTLR4 ROC in prediction model of EOS was 0.888 (95% CI: 0.840, 0.926), while the sensitivity and specificity were respectively 0.861 (95% CI: 0.837, 0.882) and 0.768 (95% CI: 0.717, 0.804). Conclusions The higher levels of HMGB1 and sTLR4 in parturient were related to HCA and EOS, which would be expected to be the early clinical indexes of HCA or EOS.