内质网应激在缺氧诱导子痫前期胎盘滋养细胞模型中调控凋亡的作用及机制  

Role and mechanism of endoplasmic reticulum stress in regulating the apoptosis of hypoxia induced preeclampsia trophoblasts

作　　者：冒丽静 诸静 袁园 刘海云 MAO Lijing;ZHU Jing;YUAN Yuan;LIU Haiyun(Department of Obstetrics and Gynecology,Nantong Maternal and Child Health Hospital,Nantong,Jiangsu 226000,China)

机构地区：[1]南通市妇幼保健院妇产科,江苏南通226000

出　　处：《徐州医科大学学报》2024年第1期6-11,共6页Journal of Xuzhou Medical University

摘　　要：目的研究内质网应激(ERS)在体外缺氧诱导子痫前期(PE)滋养细胞模型中调控凋亡的作用及机制。方法收集PE胎盘和健康胎盘,检测细胞凋亡率及ERS标志基因:葡萄糖调节蛋白78(GRP78)、ERS凋亡基因C/EBP同源蛋白(CHOP)、磷酸化JNK(p-JNK)、含半胱氨酸的天冬氨酸蛋白水解酶-12(Cleaved caspase-12)的表达水平。培养胎盘滋养细胞HTR8/SVneo,采用低氧(1%O_(2))处理24 h诱导PE细胞模型,采用ERS激动剂处理细胞,在PE细胞模型诱导过程中转染CHOP siRNA或给予JNK拮抗剂、Caspase-12抑制剂,检测细胞增殖水平(D值)、凋亡率及GRP78、CHOP、p-JNK、Cleaved caspase-12的表达水平。结果PE胎盘细胞凋亡率及GRP78、CHOP、p-JNK、Cleaved caspase-12的表达水平高于健康胎盘(P<0.05),且细胞凋亡率与GRP78、CHOP、p-JNK、Cleaved caspase-12的表达水平呈正相关;PE组及ERS激动剂组细胞的D值低于对照组,凋亡率及GRP78、CHOP、p-JNK、Cleaved caspase-12的表达水平高于对照组(P<0.05);缺氧诱导PE模型过程中转染CHOP siRNA降低CHOP表达,给予JNK拮抗剂降低p-JNK表达,给予Caspase-12抑制剂降低Cleaved caspase-12表达后,细胞D值升高,凋亡率及GRP78的表达水平降低(P<0.05)。结论缺氧诱导PE滋养细胞模型中ERS,通过CHOP、JNK和Caspase-12介导细胞凋亡。Objective To study the role and mechanism of endoplasmic reticulum stress(ERS)in regulating the apoptosis of hypoxia-induced preeclampsia(PE)trophoblasts in vitro.Methods PE placenta and healthy placenta were collected,and then the apoptosis rate and the levels of ERS marker gene glucose regulated protein 78(GRP78),ERS apoptosis gene C/EBP homologous protein(CHOP),phosphorylated JNK(p-JNK)and Cleaved caspase-12 were examined.The placental trophoblasts HTR8/SVneo were cultured.A PE cell model was induced by exposing to low oxygen(1%O_(2))for 24 h.The cells were treated with ERS agonists.During the induction of the PE cell model,the cells were transfected with CHOP siRNA or treated with JNK inhibitor and Caspase-12 inhibitor.Cell proliferation(D value),apoptosis rate and the levels of GRP78,CHOP,p-JNK and Cleaved caspase-12 were measured.Results The apoptosis rate and the levels of GRP78,CHOP,p-JNK and Cleaved caspase-12 in PE placenta were higher than those in healthy placenta(P<0.05).Cell apoptosis rate was positively correlated with the levels of GRP78,CHOP,p-JNK,and Cleaved caspase-12.The D value of cells in the PE group and ERS agonist group were lower than those in the control group,and the apoptosis rate and the the levels of GRP78,CHOP,p-JNK and Cleaved caspase-12 were higher than those in the control group(P<0.05).Transfection of CHOP siRNA reduced CHOP expression,JNK inhibitor reduced p-JNK expression,and Caspase-12 inhibitor reduced Cleaved caspase-12 expression in the hypoxia-induced PE model,leading to increased D value,reduced apoptosis rate,and lowered GRP78 expression(P<0.05).Conclusions ERS mediates cell apoptosis through CHOP,JNK,and Caspase-12 in the hypoxia-induced PE trophoblast model.

关 键 词：子痫前期 内质网应激 胎盘 滋养细胞 凋亡 

分 类 号：R714.25[医药卫生—妇产科学]