母体循环血清TLR-1、2、4、6水平与胎膜早破及亚临床绒毛膜羊膜炎关系的研究-东南大学学报医学版

母体循环血清TLR-1、2、4、6水平与胎膜早破及亚临床绒毛膜羊膜炎关系的研究

单位：1. 北京市平谷区医院妇产科, 北京 101200;
2. 北京市平谷区医院病理科, 北京 101200

分类号：R714.25

出版年·卷·期（页码）：2021·40·第一期（33-41）

摘要：

目的：研究母体循环血清Toll样受体-1（Toll-like receptor 1，TLR-1）、TLR-2、TLR-4、TLR-6水平与胎膜早破（PROM）及亚临床绒毛膜羊膜炎的关系。方法：收集2019年1月至12月本院520例PROM孕妇（PROM组），包括249例足月（tPROM组）孕妇和271例未足月（pPROM组）孕妇。另外各选取50例未足月和足月正常分娩孕妇作为对照组。收集入院时孕妇的血清样本以及新鲜胎膜组织标本。ELISA法检测血清TLR-1、2、4、6水平；qRT-PCR法和免疫组化法检测胎膜组织中TLR-1、2、4、6 mRNA及蛋白的表达。根据组织病理学检测，诊断PROM孕妇是否合并亚临床绒毛膜羊膜炎。结果：与对照组相比，PROM组孕妇血清和胎膜组织TLR-2、TLR-4表达升高（P<0.05），且PROM孕妇血清TLR-1、2、4、6水平与胎膜组织中相应的mRNA表达量呈正相关（P<0.001）。根据组织病理学诊断，tPROM组和pPROM组分别有53例（21.29%）及116例（42.80%）孕妇合并亚临床绒毛膜羊膜炎。与未合并亚临床绒毛膜羊膜炎孕妇相比，合并亚临床绒毛膜羊膜炎的孕妇血清TLR-2、TLR-4水平均升高（P<0.05）。经多因素Logistic回归分析，血清TLR-2、TLR-4水平升高是发生亚临床绒毛膜羊膜炎的独立危险因素（P<0.05）；且两者用于预测tPROM孕妇和pPROM孕妇是否合并亚临床绒毛膜羊膜炎，ROC曲线下面积分别为0.657（95%CI：0.579~0.743）、0.668（95%CI：0.584~0.759）以及0.793（95%CI：0.711~0.918）、0.813（95%CI：0.725~0.942）。结论：孕妇血清TLR-2、TLR-4水平升高与PROM以及合并亚临床绒毛膜羊膜炎有关。检测血清TLR-2、TLR-4水平对于PROM合并亚临床绒毛膜羊膜炎有一定的早期预测价值。

Objective: To investigate the relationship between maternal circulating serum toll like receptor 1(TLR-1), TLR-2, TLR-4, TLR-6 levels and premature rupture of membranes(PROM) or subclinical chorioamnionitis. Methods: 520 PROM pregnant women(PROM group), including 249 term(tPROM group) pregnant women and 271 preterm(pPROM group) pregnant women, were enrolled from January 2019 to December 2019 in our hospital. In addition, 50 term and 50 preterm pregnant women with normal delivery were selected into control group. Serum samples at admission and fresh fetal membranes after delivery were collected. The serum levels of TLR-1,-2,-4,-6 were detected by ELISA; mRNA and protein expressions of TLR-1,-2,-4,-6 in fetal membranes were detected by qRT-PCR and immunohistochemistry. According to the histopathological examination, the diagnosis of subclinical chorioamnionitis was performed in PROM pregnant women. Results: Compared with the control group, the levels of TLR-2 and TLR-4 in serum or fetal membranes were significantly increased in PROM group(P<0.05). The serum levels of TLR-1,-2,-4,-6 were positively correlated with the relative expression of TLRs mRNA in fetal membranes(P<0.001). According to the histopathological diagnosis, 53 cases(21.29%) in tPROM group and 116 cases(42.80%) in pPROM group had subclinical chorioamnionitis. Compared with the pregnant women without subclinical chorioamnionitis, the serum levels of TLR-2 and TLR-4 in tRPOM or pPROM pregnant women with subclinical chorioamnionitis were significantly higher(P<0.05). Multivariate logistic regression analysis showed that the increased serum TLR-2 and TLR-4 were the independent risk factors of subclinical chorioamnionitis(P<0.05). The area under ROC curve of serum TLR-2 and TLR-4 for predicting subclinical chorioamnionitis in tPROM or pPROM pregnant women were 0.657(95% CI:0.579-0.743), 0.668 (95% CI:0.584-0.759) and 0.793 (95% CI:0.711-0.918), 0.813 (95% CI:0.725-0.942), respectively. Conclusion: The increase of serum TLR-2 and TLR-4 levels is related with PROM or subclinical chorioamnionitis, which mainly reflects the activation of TLR-2 and TLR-4 in fetal membranes of PROM pregnant women. The detection of serum TLR-2 and TLR-4 levels has an early predictive value for PROM complicated with subclinical chorioamnionitis.

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