Zhu Aibing, Yang Jianping
Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of Anesthesiology, The Affiliated Wuxi Matemity and Child Health Care Hospital of Nanjing Medical University, Wuxi 214002, China.
Evid Based Complement Alternat Med. 2022 Feb 23;2022:6153279. doi: 10.1155/2022/6153279. eCollection 2022.
Endometrial injury is a common female disease. This study was designed to illustrate the effects of oxycodone on mifepristone-induced human endometrial stromal cells (hEndoSCs) injury and delineate the underlying molecular mechanism. hEndoSCs were stimulated with mifepristone to generate the endometrial injury in vitro model. hEndoSCs viability, cytotoxicity, and apoptosis were measured by methyl thiazolyl tetrazolium (MTT) assay, lactate dehydrogenase assay (LDH), and flow cytometry (FCM) analysis, respectively. Meanwhile, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to evaluate gene and protein expressions. The secretions of inflammatory cytokines (TNF-, IL-1, and IL-6) were measured using enzyme-linked immunosorbent assay (ELISA). The data revealed that mifepristone exposure memorably inhibited hEndoSCs viability and promoted cell apoptosis and inflammatory cytokines secretion, and oxycodone had no cytotoxicity on hEndoSCs. Oxycodone increased hEndoSCs growth, blocked cell apoptosis, enhanced Bcl-2 expression, reduced Bax levels, and decreased the secretion of inflammatory cytokines in mifepristone-induced hEndoSCs, exhibiting the protective effects in endometrial injury. In addition, the TLR4/NF-B pathway-related protein levels (TLR4 and p-p65) in mifepristone-treated hEndoSCs were enhanced, while these enhancements were inhibited by oxycodone treatment. In conclusion, oxycodone exhibited the protective role in mifepristone-triggered endometrial injury via inhibiting the TLR4/NF-B signal pathway.
子宫内膜损伤是一种常见的女性疾病。本研究旨在阐明羟考酮对米非司酮诱导的人子宫内膜基质细胞（hEndoSCs）损伤的影响，并阐明其潜在的分子机制。用米非司酮刺激hEndoSCs以建立体外子宫内膜损伤模型。分别通过甲基噻唑基四氮唑（MTT）法、乳酸脱氢酶测定（LDH）和流式细胞术（FCM）分析来检测hEndoSCs的活力、细胞毒性和凋亡情况。同时，进行定量逆转录聚合酶链反应（RT-qPCR）和蛋白质免疫印迹分析以评估基因和蛋白质表达。使用酶联免疫吸附测定（ELISA）来检测炎性细胞因子（TNF-α、IL-1和IL-6）的分泌。数据显示，米非司酮处理显著抑制hEndoSCs活力，促进细胞凋亡和炎性细胞因子分泌，而羟考酮对hEndoSCs无细胞毒性。羟考酮可促进米非司酮诱导的hEndoSCs生长，抑制细胞凋亡，增强Bcl-2表达，降低Bax水平，并减少炎性细胞因子分泌，对子宫内膜损伤具有保护作用。此外，米非司酮处理的hEndoSCs中TLR4/NF-κB信号通路相关蛋白水平（TLR4和p-p65）升高，而羟考酮处理可抑制这些升高。总之，羟考酮通过抑制TLR4/NF-κB信号通路对米非司酮引发的子宫内膜损伤发挥保护作用。
