Zeng Guihong, Zou Weiyang, Liu Changdi, Chen Yulan, Wen Tingmei
Department of Gynecology and Obstetrics, Fuyong People's Hospital, Shenzhen, China.
Department of Clinical Laboratory, Fuyong People's Hospital, Shenzhen, China.
Hum Exp Toxicol. 2025 Jan-Dec;44:9603271241307835. doi: 10.1177/09603271241307835.
Gestational diabetes mellitus (GDM) is a metabolic disorder that arises during pregnancy and heightens the risk of placental dysplasia. Ginsenoside Re (Re) may stabilize insulin and glucagon to regulate glucose levels, which may improve diabetes-associated diseases. This study aims to investigate the mechanism of Re in high glucose (HG)-induced apoptosis of trophoblasts through endoplasmic reticulum stress (ERS)-related protein CHOP/GADD153. Human trophoblast cells HTR-8/SVneo were treated with HG to simulate the HG environment , while normal glucose (NG) was used as the control. NG (5 mM) or HG (25 mM)-cultured HTR-8/SVneo cells were treated with 10, 20 or 40 μM Re. HG-cultured cells were treated with 5 mM ERS inducer 2-Deoxy-D-glucose (2-DG) and transfected with oe- CHO. Cell viability and apoptosis were detected by CCK-8 and flow cytometry; LDH release, superoxide dismutase (SOD), malonaldehyde (MDA) and glutathione (GSH) levels were detected using kits; the apoptosisrelated proteins and ERS-related proteins were assessed by western blot. Re (10, 20 or 40 μM) had no significant effect on NG-treated HTR-8/SVneo cell viability. Re (20 or 40 μM) could enhance the viability of HG-treated trophoblasts. Re (40 μM) inhibited apoptosis of HGtreated trophoblasts, ERS and alleviated oxidative stress evidenced by suppressed phosphorylation of PERK, IRE1α, reduced protein expression of ATF6, CHOP/GADD153, and inhibited MDA accumulation, GSH and SOD loss. ERS activation or CHOP/GADD153 overexpression reversed Re's inhibition on HG-induced apoptosis of trophoblasts. Re repressed HG-induced placental trophoblast apoptosis by mediating ERS-related protein CHOP/GADD153.
妊娠期糖尿病（GDM）是一种在孕期出现的代谢紊乱疾病，会增加胎盘发育异常的风险。人参皂苷Re（Re）可能使胰岛素和胰高血糖素稳定，从而调节血糖水平，这可能改善糖尿病相关疾病。本研究旨在通过内质网应激（ERS）相关蛋白CHOP/GADD153来探究Re在高糖（HG）诱导的滋养层细胞凋亡中的作用机制。用人绒毛膜滋养层细胞HTR-8/SVneo进行HG处理以模拟HG环境，而正常葡萄糖（NG）用作对照。将用NG（5 mM）或HG（25 mM）培养的HTR-8/SVneo细胞用10、20或40 μM的Re处理。用5 mM ERS诱导剂2-脱氧-D-葡萄糖（2-DG）处理HG培养的细胞，并转染oe-CHO。通过CCK-8和流式细胞术检测细胞活力和凋亡；使用试剂盒检测乳酸脱氢酶（LDH）释放、超氧化物歧化酶（SOD）、丙二醛（MDA）和谷胱甘肽（GSH）水平；通过蛋白质印迹法评估凋亡相关蛋白和ERS相关蛋白。Re（10、20或40 μM）对NG处理的HTR-8/SVneo细胞活力无显著影响。Re（20或40 μM）可增强HG处理的滋养层细胞的活力。Re（40 μM）抑制HG处理的滋养层细胞的凋亡、ERS，并减轻氧化应激，表现为PERK、IRE1α磷酸化受到抑制，ATF6、CHOP/GADD153蛋白表达降低，MDA积累受到抑制，GSH和SOD损失减少。ERS激活或CHOP/GADD153过表达可逆转Re对HG诱导的滋养层细胞凋亡的抑制作用。Re通过介导ERS相关蛋白CHOP/GADD153抑制HG诱导的胎盘滋养层细胞凋亡。
