胎膜早破产妇血清SFRP5，TIMP-1 和HMGB1 水平与并发组织学绒毛膜羊膜炎的相关性研究

目的　探讨胎膜早破（premature rupture of membranes，PROM）产妇血清分泌型卷曲相关蛋白5（secretedfrizzled-related protein-5，SFRP5）、基质金属蛋白酶组织抑制剂 1（tissue inhibitor of metalloproteinase 1，TIMP- 1）和高迁移率族蛋白B1（high mobility group protein B1，HMGB1）水平与组织学绒毛膜羊膜炎（histologic chorioamnionitis，HCA）的关系。方法　选择2019 年6 月～ 2021 年8 月河北生殖妇产医院产科收治的72 例足月PROM 并发HCA 产妇（HCA 组），120 例足月PROM 未发生HCA 产妇（非HCA 组）和51 例足月妊娠未发生PROM 产妇（对照组）。检测血清SFRP5，TIMP-1 和HMGB1 水平，分析其与PROM 产妇发生HCA 的关系。绘制受试者工作特征（ROC）曲线，分析SFRP5，TIMP-1 和HMGB1 诊断PROM 产妇发生HCA 的价值。结果　HCA 组血清SFRP5（7.53±1.42 mg/L）和TIMP-1（102.35±16.67 ng/ml ）水平低于非HCA 组（10.23±2.11 mg/L，185.23±29.42 ng/ml）和对照组（15.23±3.06mg/L，242.13±32.65 ng/ml），差异均有统计学意义（F =187.726, 423.352，均P ＜ 0.05）；血清HMGB1 水平（10.25±3.26ng/ml）高于非HCA 组（6.02±1.41 ng/ml）和对照组（3.06±0.81 ng/ml），差异有统计学意义（F=191.968，P ＜ 0.05）。多因素Logistic 回归分析示PROM 破膜时间≥ 48hOR=2.208，95 ％ CI=1.466 ～ 3.326）]， 阴道检查次数≥ 3 次OR=1.540，95％ CI=1.206 ～ 1.968）]，SFRP5 ＜ 7.53mg/LOR=1.657，95％ CI=1.220 ～ 2.250）]，TIMP-1 ＜ 102.35ng/mlOR=1.826，95 ％ CI=1.275 ～ 2.613）] 和HMGB1 ≥ 10.25ng/mlOR=1.809，95 ％ CI=1.237 ～ 2.647] 是PROM 产妇发生HCA 的危险因素（均P ＜ 0.05）。SFRP5，TIMP-1 和HMGB1 诊断足月PROM 产妇发生HCA 的曲线下面积分别为0.707，0.731 和0.747，联合诊断曲线下面积为0.933，高于单独指标（Z=5.822，5.611，5.274，均P=0.000）。结论　PROM 产妇血清SFRP5 和TIMP-1 水平降低，HMGB1 水平升高，且与HCA 发病密切相关。SFRP5，TIMP-1 和HMGB1 可作为HCA 诊断的生物标志物。

Correlation of Serum SFRP5, TIMP-1 and HMGB1 Levels with Histological Chorioamnitis in Pregnant Women with Premature Rupture of Membranes

Objective　To investigate the relationship between serum secreted frizzled-related protein-5 (SFRP5), tissue inhibitor of metalloproteinase 1 (TIMP-1), high mobility group protein B1 (HMGB1) and histologic chorioamnionitis (HCA) in pregnant women with premature rupture of membranes (PROM).Methods　From June 2019 to August 2021, 72 cases of full-term PROM with HCA (HCA group), 120 cases of full-term PROM without HCA (non-HCA group) and 51 cases of full-term pregnancy without PROM (control group) from Hebei Maternity Hospital were selected.Serum level of SFRP5, TIMP-1 and HMGB1 were detected to analyze the relationship between SFRP5, TIMP-1 and HMGB1 and HCA in PROM parturient women.Receiver operating characteristic curve (ROC) was drawn to analyze the value of SFRP5, TIMP-1 and HMGB1 in diagnosing HCA in PROM parturient. Results　The levels of serum SFRP5 （7.53±1.42 mg/L）and TIMP-1（102.35±16.67 ng/ml）in HCA group were lower than those in non-HCA group（10.23±2.11 mg/L，185.23±29.42 ng/ml）and control group（15.23±3.06mg/L，242.13±32.65 ng/ml）, the differences were statistically significant （F =187.726, 423.352，all P ＜ 0.05）, and the levels of serum HMGB1 （10.25±3.26 ng/ml）were higher than those in non-HCA group （6.02±1.41 ng/ml）and control group （3.06±0.81 ng/ml），the difference was statistically significant（F=191.968，P ＜ 0.05）.Multivariate Logistic regression analysis showed that PROM rupture time ≥ 48h OR=2.208，95%CI=1.466 ～ 3.326）], vaginal examination times ≥ 3OR=1.540，95%CI=1.206 ～ 1.968）], SFRP5 ＜ 7.53mg/LOR=1.657，95%CI=1.220 ～ 2.250）]，TIMP-1 ＜ 102.35ng/ mlOR=1.826，95%CI=1.275 ～ 2.613）] and HMGB1 ≥ 10.25ng/mlOR=1.809，95%CI=1.237 ～ 2.647] were risk factors for HCA in PROM parturient women（ all P＜0.05）.The area under the curve of SFRP5, TIMP-1 and HMGB1 were 0.707, 0.731 and 0.747, respectively, and the area under the curve of SFRP5, TIMP-1 and HMGB1 were 0.933, higher than the single index (Z=5.822, 5.611 and 5.274, all P ＜ 0.05). Conclusion　The serum levels of SFRP5 and TIMP-1 in PROM maternal decreased, while the serum level of HMGB1 increased, which were closely related to the pathogenesis of HCA. SFRP5, TIMP-1 and HMGB1 can be used as biomarkers for the diagnosis of HCA.