早、晚发型重度子痫前期胎盘组织内质网应激及滋养细胞凋亡相关标志物的表达水平分析  

Analysis of expression levels of endoplasmic reticulum stress and trophoblast apoptosis-related markers in placental tissues of early and late-onset severe preeclampsia

作　　者：康芬 吴永远 李晓兰 Kang Fen;Wu Yongyuan;Li Xiaolan(Dept of Obstetrics and Gynecology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract,Hefei 230022;MOE Key Laboratory of Population Health Across Life Cycle,Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院妇产科,合肥230022 [2]国家卫生健康委配子及生殖道异常研究重点实验室,合肥230022 [3]出生人口健康教育部重点实验室(安徽医科大学),合肥230022

出　　处：《安徽医科大学学报》2025年第1期102-108,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81801477);安徽医科大学第一附属医院梯队人才及学术带头人培养对象资助经费(编号:1310)。

摘　　要：目的探讨早、晚发型重度子痫前期(SPE)和正常妊娠孕妇胎盘组织中内质网应激(ERS)和滋养细胞凋亡相关标志物的表达水平与SPE的相关性。方法收集医院就诊的早、晚发型SPE单胎孕妇的胎盘组织各20例(早发组、晚发组),选择同期在该院分娩的血压正常无其它妊娠并发症的孕妇20例作为正常组。透射电镜观察胎盘组织中滋养细胞内质网的超微结构,蛋白质印迹实验检测胎盘组织中ERS相关蛋白的表达水平[葡萄糖调节蛋白78(GRP78)、C/EBP同源蛋白(CHOP)、磷酸化真核翻译起始因子2α(p-eIF2α)和磷酸化肌醇需求酶1(p-IRE1)α],免疫组化法检测胎盘组织中增殖标志物增殖细胞核抗原(Ki67)的表达,TUNEL染色检测胎盘组织滋养细胞凋亡情况。结果正常孕妇组胎盘组织中滋养细胞内质网体积正常,无扩张和肿胀。而SPE组胎盘组织内质网出现明显水肿,呈现显著扩张的状态,且早发组比晚发组扩张明显;与正常组相比,早发组和晚发组胎盘组织中ERS相关蛋白GRP78(P<0.001,P<0.05)和CHOP(P<0.01,P<0.001)的表达水平及eIF2α(P<0.0001,P<0.01)、IRE1α(P<0.0001,P<0.001)磷酸化水平增加,p-eIF2α/eIF2α(P<0.001)和p-IRE1α/IRE1α(P<0.05)比值及GRP78蛋白(P<0.01)表达水平在早发组中均高于晚发组;与正常组相比,早发组和晚发组每个视野下Ki67阳性细胞数减少(P<0.0001,P<0.05),早发组胎盘Ki67阳性细胞数少于晚发组(P<0.01);早发组胎盘组织中每个视野阳性凋亡细胞多,滋养细胞凋亡率高于其他两组(P<0.001,P<0.01)。结论SPE患者胎盘组织滋养细胞凋亡增加和增殖受抑制可能与ERS过度激活相关,其在早发型SPE患者胎盘组织中激活水平高于晚发组。Objective To explore the correlation between the expression levels of endoplasmic reticulum stress(ERS)and trophoblast apoptosis-related markers and severe preeclampsia(SPE)in placental tissues of pregnant women with early-and late-onset SPE and normal pregnancy.Methods Placental tissues from 20 early and late haired severe preeclamptic singleton pregnant women who attended the Hospital were collected(early-onset group,late-onset group),and 20 cases pregnant women of normal blood pressure and no other pregnancy complications who delivered in our hospital during the same period were selected as the normal group.Transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum of trophoblast cells in placental tissues.Protein blotting assay was used to detect the expression levels of endoplasmic reticulum stress-related proteins,including Glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP),Phosphorylated eukaryotic translation initiation factor 2α(p-eIF2α)and Phosphatidylinositol-requiring enzyme 1(p-IRE1)α.Immunohistochemistry assay was used to detect the expression of proliferating cell nuclear antigen(Ki67),a proliferation marker,in placental tissues,and TUNEL staining was used to detect placental tissue trophoblast apoptosis.Results The endoplasmic reticulum of trophoblast cells in the placental tissues of the normal pregnant women group was normal in volume,with no dilatation or swelling.In contrast,the endoplasmic reticulum of placental tissues in the severe preeclampsia group showed obvious edema and significant dilatation,and the dilatation was more obvious in the early-onset group than in the late-onset group.The expression level of endoplasmic reticulum stress-related proteins GRP78(P<0.001,P<0.05)and CHOP(P<0.01,P<0.001),the phosphorylation levels of eIF2α(P<0.0001,P<0.01)and IRE1α(P<0.0001,P<0.001)increased in placental tissues of both early-onset and late-onset groups compared to those of the normal group.The p-eIF2α/eIF2α(P<0.001)to p-IRE1α/IRE

关 键 词：子痫前期 胎盘 内质网应激 增殖 凋亡 孕周 

分 类 号：R714.25[医药卫生—妇产科学]