【摘要】 目的研究白藜芦醇-Sirt1-Foxo1调控通路对缺氧心肌细胞的保护作用。方法将大鼠心肌细胞株H9C2培养48h后,随机分为5组,即20μmol/L白藜芦醇(resveratro,lRes)干预组、二甲基亚砜(dimethylsulfoxide,DMSO)对照组、40mmol/L尼克酰胺(nicotinamide,Nam)干预组、Nam空白对照组及正常对照组。培养24h后终止培养,用RT-PCR法和免疫细胞化学染色法检测Sirt1、Foxo1、p27、BimmRNA及其蛋白表达水平的变化;用TUNEL法及流式细胞仪(flowcytometer,FCM)分析细胞凋亡和细胞周期。结果20μmol/LRes干预组可使Sirt1mRNA及SIRT1蛋白表达的水平增加。Sirt1可通过抑制Foxo1mRNA的转录活性而调节其下游基因p27及Bim的表达。SIRT1的高表达可使细胞周期延长,细胞凋亡减少。结论Res干预可使SIRT1表达增加。Sirt1可能通过对Foxo1及其下游基因Bim、p27的调控,延长心肌细胞的细胞周期,减少其凋亡。Protectiveeffectofresveratrol-Sirt1-Foxo1pathwayonanoxiccardiocytes更多还原

【Abstract】 AIM To study the protective effect of resveratrolSirt1Foxo1 pathway on anoxic cardiocytes. METHODS H9C2 embryonal rat heartderived cells were randomly divided into five groups: 20 μmol/L resveratrol (Res) group, dimethyl sulfoxide (DMSO) group, 40 mmol/L nicotinamide (Nam) group, Nam control group and normal control group. After the 24hour culture, the expressions of Sirt1, Foxo1, p27, Bim mRNA and their proteins were respectively detected using RTRCR and the immunocytochemical staining. The apotosis and cell cycle of H9C2 cells were analyzed by TUNEL staining followed by flow cytometry(FCM). RESULTS The expression of Sirt1 mRNA and protein increased after incubation with 20 μmol/L resveratrol. Sirt1 regulated p27 and Bim by inhibiting the transcription activity of Foxo1. More cells were arrested at the G0+G1 checkpoint and cell apoptosis decreased after treatment with resveratrol. CONCLUSION Res promotes the expression of Sirt1 and Sirt1 protects the cardiomyocytes from hypoxiainduce apoptosis and promotes cell cycle arrest, which may be implemented by the regulation of Foxo1 and its downstream genes such as Bim and p27.更多还原