孕妇血清sRAGE与氧化应激及炎症的关系及其在早产中的作用

黄科华 颜建英 徐榕莉 罗金英 陈娴

【摘要】 目的：探討孕妇血清糖基化终产物可溶性受体（sRAGE）水平变化在自发性早产发病中的作用及其与氧化应激、炎症反应的关系。方法：选择2019年1-12月在本院产科住院分娩的20例自发性早产孕妇作为病例组，另选取同期足月妊娠经阴道顺产孕妇20例作为对照组。采用酶联免疫吸附试验（ELISA）检测孕妇血清sRAGE水平及炎性因子水平，记录临床相关指标。体外分离培养早产胎盘滋养细胞并分组，分别用不同浓度sRAGE干预，应用氧化应激检测试剂盒检测干预12、24 h后各组细胞活性氧自由基（ROS）、总超氧化物歧化酶（T-SOD）含量。结果：病例组临产后血清sRAGE水平低于对照组，而肿瘤坏死因子（TNF-α）水平、白细胞计数（WBC）、中性粒细胞计数（N）、中性粒细胞/淋巴细胞（NLR）、C反应蛋白（CRP）均高于对照组，差异均有统计学意义（P<0.05）。血清sRAGE水平与TNF-α、WBC、NLR、N、CRP均呈负相关（P<0.01）。添加sRAGE处理后，12 h收样组T-SOD含量随着sRAGE浓度升高而上升，ROS含量随着sRAGE浓度升高而下降（P<0.05）;24 h收样组，0.6 μg/mL的sRAGE处理后细胞样本中的T-SOD、ROS含量与0 μg/mL的比较，差异均无统计学意义（P>0.05）;1.2 μg/mL的sRAGE处理后细胞样本中的T-SOD含量上升，ROS含量下降（P<0.05）。结论：孕妇血清sRAGE水平升高是自发性早产的保护因素，机制与孕妇炎症反应及胎盘滋养细胞氧化应激损伤有关，sRAGE对胎盘滋养细胞氧化应激损伤的保护作用存在时间与浓度依赖性。

【关键词】 早产 糖基化终产物可溶性受体 氧化应激 炎性因子

Relationship between Serum sRAGE of Pregnant Women and Oxidative Stress and Inflammation and Roles in Preterm Labor/HUANG Kehua， YAN Jianying， XU Rongli， LUO Jinying， CHEN Xian. //Medical Innovation of China， 2021， 18（13）： 00-007

[Abstract] Objective： To explore the role of soluble receptors for advanced glycation end products （sRAGE） in pregnant women in the onset of spontaneous preterm labor and its relationship with oxidative stress and inflammation. Method： A total of 20 spontaneous preterm pregnant women who delivered in obstetrics department of our hospital from January to December 2019 were selected as the case group， 20 pregnant women with vaginal delivery during the same term pregnancy were selected as control group. Serum sRAGE levels and inflammatory factors of pregnant women were detected by enzyme-linked immunosorbent assay （ELISA）， and clinical related indexes were recorded. Premature placental trophoblast cells were isolated and cultured in vitro and divided into groups. The cells were treated with differences concentrations of sRAGE， respectively. The content of reactive oxygen species （ROS） and total superoxide dismutase （T-SOD） in each group were detected by the oxidative stress detection kit after 12 and 24 h intervention. Result： The level of serum sRAGE in the case group was lower than that in the control group， while the level of tumor necrosis factor （TNF-α）， white blood cell count （WBC）， neutrophil count （N）， neutrophil/lymphocyte （NLR） and C-reactive protein （CRP） in the case group were higher than those in the control group， the differences were statistically significant （P<0.05）. Serum sRAGE level was negatively correlated with TNF-α， WBC， NLR， N and CRP （P<0.01）. After adding sRAGE treatment， the T-SOD content in 12 h sampling group increased with the increase of sRAGE concentration， while the ROS content decreased with the increase of sRAGE concentration （P<0.05）. There were no significant differences in T-SOD and ROS contents between 0.6 μg/mL sRAGE and 0 μg/mL sRAGE in 24 h sampling group （P>0.05）. The content of T-SOD and ROS in cell samples were increased and decreased after 1.2 μg/mL sRAGE treatment （P<0.05）. Conclusion： The increase of serum sRAGE level in pregnant women is a protective factor for spontaneous preterm delivery， and the mechanism is related to the inflammatory response in pregnant women and the oxidative stress injury of placental trophoblast cells. The protective effect of sRAGE on the oxidative stress injury of placental trophoblast cells is time and concentration dependent.

[Key words] Preterm labor Soluble receptors for advanced glycation end products Oxidative stress Inflammatory factors

First-authors address： Fujian Maternity and Child Hospital， Fuzhou 350000， China

doi：10.3969/j.issn.1674-4985.2021.13.001

早产（preterm labor， PTL）是导致围生儿发病和死亡的重要原因。研究显示全球约60%的早产发生在发展中国家[1]，我国各地区早产的发生率达6%～10%[2]。根据早产的病因，可以分为医疗性早产和自发性早产，临床中80%的早产为自发性。自发性早产是一种多因素综合征，其具体的发病机制尚不明确。晚期糖基化终产物受体（receptor for advanced glycation end-products， RAGE）能够与许多配体结合，如晚期糖基化终产物（advanced glycation end products，AGEs）等，在疾病的发生和发展中起重要作用。可溶性RAGE（soluble receptors for advanced glycation end-products， sRAGE）可与RAGE竞争结合配体，阻断RAGE诱导的细胞内信号传导途径，从而阻止疾病的发生发展。……