[1]王海臻,蔡丹纯,廖丹丹,等.内质网应激介导滋养细胞凋亡在妊娠期肝内胆汁淤积症中的作用及机制[J].南方医科大学学报,2018,(05):572.
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内质网应激介导滋养细胞凋亡在妊娠期肝内胆汁淤积症中的作用及机制()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2018年05期
页码:
572
栏目:
出版日期:
2018-05-15

文章信息/Info

Title:
Role of endoplasmic reticulum stress- induced apoptosis of trophoblasts in intrahepatic cholestasis during pregnancy
作者:
王海臻蔡丹纯廖丹丹钟梅高云飞盛超
关键词:
妊娠期肝内胆汁淤积症去氧胆酸内质网应激凋亡
Keywords:
intrahepatic cholestasis of pregnancy deoxycholic acid endoplasmic reticulum stress apoptosis
摘要:
目的探讨内质网应激介导滋养细胞凋亡在妊娠期肝内胆汁淤积症(ICP)中的作用及机制。方法收集2015 年12 月~ 2016年12月在南方医科大学南方医院住院分娩的ICP孕妇20例为病例组,另以同期因社会因素行择期剖宫产术的20例无合 并症的正常孕妇为正常对照组。利用HE染色计量观察正常对照孕妇及ICP孕妇胎盘合体细胞结节数量;RT-PCR法检测正常 孕妇及ICP孕妇胎盘组织中GRP78、CHOP、caspase-3及caspase-7的mRNA表达;建立不同浓度胆酸(0、10、50、100 μmol/L)体 外刺激HTR-8/SVneo人早孕滋养细胞株模型,利用RT-PCR法检测HTR-8/SVneo细胞GRP78、CHOP、caspase-3及caspase-7的 mRNA表达及利用蛋白印迹法检测GRP78、CHOP蛋白的表达;caspase-3、caspase-7活性检测试剂盒分别检测其活化程度;电镜 观察细胞凋亡形态。结果ICP 组较对照组孕妇胎盘组织中合体细胞结节数明显增多(P<0.01);GRP78、CHOP、caspase-3 及 caspase-7的mRNA表达明显上调(P<0.05);不同浓度(0、10、50、100 μmol/L)去氧胆酸作用细胞24 h后,GRP78、CHOP、caspase-3 及caspase-7 mRNA的表达水平较对照组显著增高(P<0.05),GRP78、CHOP蛋白的表达水平较对照组也显著增高,且均存在浓 度依赖效应;50 μmol/L去氧胆酸作用细胞24 h后检测caspase-3及caspase-7活性增高(P<0.05);50 μmol/L去氧胆酸作用细胞 12 h后电镜观察HTR-8/SVneo细胞呈现凋亡小体。结论ICP孕妇胎盘组织中存在滋养细胞过度凋亡及内质网应激激活的现 象。去氧胆酸可以呈浓度依赖性地促进滋养细胞内质网应激相关基因mRNA和蛋白的表达,引起细胞凋亡,提示内质网应激介 导的滋养细胞凋亡在ICP的发病机制中可能起着重要的作用。
Abstract:
Objective To investigate the role of endoplasmic reticulum stress (ERS)- induced trophoblast apoptosis in the development of intrahepatic cholestasis during pregnancy (ICP). Methods Twenty pregnant women with ICP and 20 normal pregnant women undergoing cesarean section were enrolled in this study. The number of placenta syncytial knots in these women was determined using HE staining. The mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 were detected using RT-PCR in the placental tissues of the women and also in HTR-8/SVneo cells treated with different doses of deoxycholic acid (DCA). Caspase-3 and caspase-7 activities were also detected in DCA-treated HTR-8/SVneo cells using commercial assay kits, and the presence of apoptotic bodies in the cells were detected with electron microscopy. Results Compared with normal placental tissues, the placenta from women with ICP showed significantly increased syncytial knots (P<0.01) and obviously enhanced mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 (P<0.05). In HTR-8/SVneo cells treated with different doses of DCA (0, 10, 50, and 100 μmol/L), the mRNA expressions of GRP78, CHOP, caspase-3 and caspase-7 were significantly increased in a dose-dependent manner (P<0.05) and the protein levels of GRP78 and CHOP were also increased dosedependently. Treatment with DCA at 50 μmol/L for 24 h significantly upregulated caspase-3 and caspase-7 activity in the cells (P<0.05), and the cells treated with 50 μmol/L DCA for 12 h showed the presence of apoptotic bodies. Conclusion The activation of ERS and enhanced apoptosis of the trophoblasts occur in the placenta of women with ICP. DCA can significantly increase the expressions of ERS markers and thus lead to trophoblast apoptosis, suggesting that ERS- induced trophoblasts apoptosis may play a key role in the development of ICP.
更新日期/Last Update: 1900-01-01