Department of Cardiology, Xi'an Central Hospital, Xi'an, China.
Department of Center sterile supply, Xi'an Hospital of Traditional Chinese Medicine, Shaanxi, China.
Biomarkers. 2021 Jun;26(4):363-370. doi: 10.1080/1354750X.2021.1903999. Epub 2021 Apr 15.
Methylated CpG binding protein 2 (MeCP2) is closely associated with heart failure, but its role in I/R injury remains unclear. The purpose of this study was to explore the role and underling mechanism of MeCP2 in myocardial I/R injury. Hypoxia/reperfusion (H/R)-induced H9c2 cardiomyocytes was used to establish an I/R injury model. Oxidative stress was assessed by measuring reactive oxygen species (ROS) generation, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity. Cell viability and cell cycle arrest were evaluated by the Cell Counting Kit-8 assay and cell cycle assay, respectively. Apoptosis was determined using flow cytometry analysis. The expression of MeCP2 in H9c2 cells was decreased after H/R treatment. The overexpression of MeCP2 inhibited H/R-induced oxidative stress, cell cycle arrest and apoptosis of H9c2 cells. Moreover, MeCP2 inhibited the activation of secreted frizzled related protein 4 (SFRP4)/Wnt/β-catenin axis, and SFRP4 relieved the effect of MeCP2 on oxidative stress, cell cycle arrest and apoptosis in H/R-induced H9c2 cells. MeCP2 attenuated H/R-induced injury in H9c2 cardiomyocytes by modulating the SFRP4/Wnt/β-catenin axis, which suggested that MeCP2 might serve as a therapeutic target of patients with AMI after reperfusion.
甲基化 CpG 结合蛋白 2（MeCP2）与心力衰竭密切相关，但它在 I/R 损伤中的作用尚不清楚。本研究旨在探讨 MeCP2 在心肌 I/R 损伤中的作用及其潜在机制。采用缺氧/复氧（H/R）诱导的 H9c2 心肌细胞建立 I/R 损伤模型。通过测定活性氧（ROS）生成、丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性来评估氧化应激。通过细胞计数试剂盒-8 检测和细胞周期检测分别评估细胞活力和细胞周期停滞。通过流式细胞术分析测定细胞凋亡。H/R 处理后 H9c2 细胞中 MeCP2 的表达降低。MeCP2 的过表达抑制了 H/R 诱导的 H9c2 细胞氧化应激、细胞周期停滞和凋亡。此外，MeCP2 抑制了分泌卷曲相关蛋白 4（SFRP4）/Wnt/β-连环蛋白轴的激活，SFRP4 减轻了 MeCP2 对 H/R 诱导的 H9c2 细胞氧化应激、细胞周期停滞和凋亡的影响。MeCP2 通过调节 SFRP4/Wnt/β-连环蛋白轴减轻 H/R 诱导的 H9c2 心肌细胞损伤，这表明 MeCP2 可能成为再灌注后 AMI 患者的治疗靶点。
