激光生物学报2025，Vol.34Issue(6)：561-568,8.DOI:10.3969/j.issn.1007-7146.2025.06.010
丙泊酚基于SIRT1/p53通路介导的铁死亡对心肌细胞缺氧/复氧损伤的保护作用及机制研究
Investigation into the Protective Effects and Mechanisms of Propofol-mediated Ferroptosis via the SIRT1/p53 Pathway in Cardiomyocyte Hypoxia/Reoxygenation Injury
摘要
Abstract
To investigate the effects of propofol(Pro)on hypoxia/reoxygenation(H/R)injury in H9C2 cardiomyocytes via regulation of the silent information regulator 1(SIRT1)/p53 signaling pathway-mediated ferroptosis,an in vitro H9C2 cell H/R model was established.Cells were divided into the following groups:Control group,H/R group,H/R+Pro group,H/R+Pro+erastin group,H/R+Pro+si-NC group,and H/R+Pro+si-SIRT1 group.The cytotoxic effect of Pro on H9C2 cells was assessed using the cell counting kit-8(CCK-8)assay.Intracellular reactive oxygen species(ROS)levels were measured using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe.Mitochondrial ultrastructure was examined by transmission electron microscopy(TEM).Oxidative stress markers were quantified using corresponding assay kits.Expression levels of ferroptosis-related proteins were detected by Western blot.Results demonstrated that compared to the Control group,the H/R group exhibited significantly reduced cell viability,elevated levels of ROS and malondialdehyde(MDA),decreased levels of catalase(CAT)and superoxide dismutase(SOD),nuclear membrane rupture,increased mitochondrial membrane density,loss of mitochondrial cristae,swelling and rupture of mitochondria,increased Fe2+content and lactate dehydrogenase(LDH)activity,elevated levels of acyl-CoA synthetase long-chain family member 4(ACSL4)and p53,and reduced levels of glutathione peroxidase 4(GPX4)and SIRT1(P<0.05).Pro treatment significantly ameliorated H/R injury,increasing cell viability and elevating SOD,CAT,GPX4,and SIRT1 levels,while reducing Fe2+content,ROS,MDA,ACSL4,and p53 levels,and restoring mitochondrial structure(P<0.05).Erastin partially reversed the protective effects of Pro(P<0.05).Conversely,si-SIRT1 completely abolished the effects of Pro,resulting in decreased GPX4 levels and increased Fe2+content and ACSL4 levels(P<0.05).This study revealed that Propofol likely protects cardiomyocytes against H/R injury by activating the SIRT1/p53 pathway to inhibit ferroptosis.This finding provides crucial mechanistic insight into Propofol-mediated cardioprotection and suggests a potential novel strategy for the prevention and treatment of myocardial ischemia-reperfusion injury.关键词
丙泊酚/沉默信息调节因子1/p53信号通路/铁死亡/心肌细胞/缺氧/复氧损伤Key words
propofol/silent information regulator 1/p53 signaling pathway/ferroptosis/cardiomyocytes/hypoxia/reoxygenation injury分类
医药卫生引用本文复制引用
高蕤,胡云,木开达斯·马合木提,杨欢,陈思宇..丙泊酚基于SIRT1/p53通路介导的铁死亡对心肌细胞缺氧/复氧损伤的保护作用及机制研究[J].激光生物学报,2025,34(6):561-568,8.基金项目
新疆维吾尔自治区自然科学基金项目(2022D01C229) （2022D01C229）
国家自然科学基金项目(81960053). （81960053）
