未足月胎膜早破合并绒毛膜羊膜炎患者胎盘组织自噬相关蛋白的表达及其临床意义

Expression and clinical significance of autophagy-related proteins in placental tissues of patients with preterm premature rupture of membranes complicated by chorioamnionitis

摘要:

目的 探讨未足月胎膜早破（PPROM）合并绒毛膜羊膜炎（CA）患者胎盘组织自噬相关蛋白的表达及临床意义。方法 选取2021年1月—2024年3月安徽省妇女儿童医学中心收治的121例PPROM患者，根据分娩时胎膜组织病理检查结果分为CA组（57例）、非CA组（64例）。采用实时荧光定量聚合酶链反应测定胎盘组织中自噬相关蛋白LC3、Beclin1表达，比较两种因子在胎盘组织中的表达及相关性。结果 CA组胎盘组织自噬相关蛋白LC3、Beclin1 mRNA相对表达量均高于非CA组（P <0.05）。两组患者年龄、胎膜早破孕周、孕期体重增加、分娩孕周、孕次、流产史、生育次数、宫腔手术史、阴道出血史、宫颈机能不全、孕期吸烟或被动吸烟、孕期饮酒、伴阴道炎症、甘油三酯（TG）、总胆固醇（TC）、血肌酐、血尿酸、白细胞计数、血小板计数、红细胞计数、降钙素原水平比较，差异均无统计学意义（P >0.05）。CA组妊娠期高血压、妊娠期糖尿病、中性粒细胞、C反应蛋白水平均高于非CA组（P <0.05）。多因素逐步Logistic回归分析结果显示：Beclin1 mRNA相对表达量［O^R=3.991（95% CI：1.193，13.353）］、LC3 mRNA相对表达量［O^R=3.734（95% CI：1.865，7.476）］、妊娠期糖尿病［O^R=5.212（95% CI：2.145，12.667）］是影响PPROM患者合并CA的危险因素（P <0.05）。受试者工作特征曲线分析结果显示，LC3 mRNA相对表达量、Beclin1 mRNA相对表达量及两者联合预测PPROM患者并发CA的敏感性分别为68.42%（95% CI：0.613，0.758）、75.44%（95% CI：0.698，0.839），84.21%（95% CI：0.706，0.885）；特异性分别为75.00%（95% CI：0.716，0.823）、71.88%（95% CI：0.627，0.790）、89.06%（95% CI：0.824，0.943）；曲线下面积分别为0.725（95% CI：0.622，0.827）、0.718（95% CI：0.604，0.831）、0.889（95% CI：0.822，0.957）。结论 自噬相关蛋白LC3、Beclin1可能参与PPROM并发CA的发生、发展，且两者联合具有较高的预测价值。

Abstract:

Objective To investigate the expression and clinical significance of autophagy-related proteins in placental tissues of patients with preterm premature rupture of membrane (PPROM) complicated by chorioamnionitis (CA).Methods The 121 patients with PPROM admitted to our hospital from January 2021 to March 2024 were divided into the CA group (57 cases) and the non-CA group (64 cases) according to the pathological findings of fetal membranes during delivery. The expressions of autophagy-related proteins LC3 and Beclin1 in placental tissues were determined by quantitative real-time polymerase chain reaction. The expressions of these two molecules in placental tissues were compared and their correlations were determined.Results The relative mRNA expression levels of autophagy-related proteins LC3 and Beclin1 in placental tissues in the CA group were higher than those in the non-CA group (P < 0.05). There were no statistically significant differences between the two groups in terms of age, gestational week at rupture of membranes, weight gain during pregnancy, gestational week at delivery, number of pregnancies, history of miscarriage, number of births, history of uterine surgery, history of vaginal bleeding, cervical insufficiency, smoking or passive smoking during pregnancy, alcohol consumption during pregnancy, presence of vaginal inflammation, levels of TG, TC, serum creatinine, and serum uric acid, white blood cell count, platelet count, red blood cell count, and procalcitonin levels (P > 0.05). The CA group had higher proportions of patients with gestational hypertension and gestational diabetes mellitus, and higher levels of neutrophils and C-reactive protein compared with the non-CA group. The multivariable Logistic regression analysis exhibited that high relative expressions of Beclin1 mRNA [O^R = 3.991 (95% CI: 1.193, 13.353) ] and LC3 mRNA [O^R = 3.734 (95% CI: 1.865, 7.476) ], and gestational diabetes mellitus [O^R = 5.212 (95% CI: 2.145, 12.667) ] were risk factors for complicating CA in patients with PPROM (P < 0.05). The receiver operating characteristic curve analysis demonstrated that the sensitivities of the relative mRNA expressions of LC3 and Beclin1 and their combination for predicting the complication of CA in PPROM were 68.42% (95% CI: 0.613, 0.758), 75.44% (95% CI: 0.698, 0.839), and 84.21% (95% CI: 0.706, 0.885), with the specificities being 75.00% (95% CI: 0.716, 0.823), 71.88% (95% CI: 0.627, 0.790) and 89.06% (95% CI: 0.824, 0.943), and the areas under the curves being 0.725 (95% CI: 0.622, 0.827), 0.718 (95% CI: 0.604, 0.831) and 0.889 (95% CI: 0.822, 0.957).Conclusions Autophagy-related proteins LC3 and Beclin1 may be involved in the occurrence and development of PPROM complicated by CA, and their combination has a high predictive value.