雌激素信号转导通路失衡与妊娠高血压疾病胎盘血管病变发生的关系  

Imbalance of estrogen signaling pathway and its relationship with placental vascular lesions in pregnancy-induced hypertension

作　　者：高倩 张爱萍 王海娜 GAO Qian;ZHANG Ai-ping;WANG Hai-na(Department of Obstetrics,Qinghai Red Cross Hospital,Xining 810000,Qinghai,China;不详)

机构地区：[1]青海红十字医院产一科,青海西宁810000 [2]青海红十字医院妇三科,青海西宁810000

出　　处：《广东医学》2023年第9期1080-1085,共6页Guangdong Medical Journal

基　　金：青海省卫生健康科研基金项目(2021-q-1265)。

摘　　要：目的探讨雌激素信号转导通路失衡在妊娠高血压疾病胎盘血管病变发生中的作用。方法建立高血压妊娠大鼠模型,分为对照组、模型组和模型+雌二醇(E_(2))组。记录母体大鼠的血压(BP)和尿蛋白水平,HE染色检测妊娠高血压大鼠胎盘病理组织,采用蛋白质印迹检测各组成纤维细胞中雌激素通道蛋白[雌激素受体α36(ERα36)、雌激素受体α(ERα)、雌激素受体β(ERβ)和G蛋白偶联雌激素受体(GPER)]、血管内皮因子[C反应蛋白(CRP)、血管内皮生长因子(VEGF)和内皮型一氧化氮合酶(eNOS)]及TLR4通路(TLR4、MyD88、p-IRAK4和TRAF6)蛋白的表达。结果与对照组比较,模型组的雌激素ERα36、ERα和ERβ表达下调,而E_(2)处理后其表达增加;此外,模型组大鼠血压及尿蛋白升高,模型组胎盘绒毛中的细胞胆细胞、绒毛数量减少,胎盘绒毛结构萎缩,部分绒毛出现纤维蛋白样坏死等,而模型+E_(2)组病理明显好转;模型组的血管内皮因子(CRP、VEGF和eNOS)及TLR4通路(TLR4、MyD88、p-IRAK4和TRAF6)表达升高,而E_(2)处理后其表达降低,差异有统计学意义(P<0.05)。结论E_(2)可以改善妊娠高血压大鼠结局。E_(2)的保护作用可以通过与ERα36结合来降低胎盘血管生成因子以及TLR4/MyD88/IRAK4/TRAF6信号转导的表达来部分发挥。Objective To investigate the role of estrogen signaling pathway imbalance in the development of placental vascular lesions in pregnancy-induced hypertension(PIH).Methods A rat model of hypertension during pregnancy was established.The rats were divided into control group,model group,and model+estradiol(E_(2))groups.Maternal blood pressure(BP)and urinary protein levels were recorded.Histopathological examination of placental tissues from PIH rats was performed using HE staining.Protein expression of estrogen receptor variants(ERα36,ERα,ERβ,and GPER),vascular endothelial factors[C-reactive protein(CRP),vascular endothelial growth factor(VEGF),and endothelial nitric oxide synthase(eNOS)],and TLR4 pathway(TLR4,MyD88,p-IRAK4,and TRAF6)were detected using Western blotting.Results Compared to the control group,the expression of estrogen receptors ERα36,ERα,and ERβwas downregulated in the model group,but increased after E_(2)treatment.Additionally,model rats exhibited elevated BP and urinary protein levels.Placental villi in the model group showed reduced cell density,decreased villous quantity,structural atrophy,and fibrous-like necrosis.E_(2)treatment ameliorated these pathological changes.Expression of vascular endothelial factors(CRP,VEGF,and eNOS)and TLR4 pathway(TLR4,MyD88,p-IRAK4,and TRAF6)were upregulated in the model group and downregulated after E_(2)treatment,with statistically significant differences(P<0.05).Conclusion E_(2)can improve the outcomes of rats with pregnancy-induced hypertension.The protective effect of E_(2)might be partially exerted by binding to ERα36,leading to the downregulation of placental vascular factors and TLR4/MyD88/IRAK4/TRAF6 signal transduction.

关 键 词：雌激素 妊娠高血压 血管内皮因子 

分 类 号：R71[医药卫生—妇产科学] R363.2[医药卫生—临床医学]