AMPK/Nrf2通路介导艾司氯胺酮对H_(2)O_(2)诱导心肌细胞损伤的保护作用  

Protective Effect of Esketamine on H_(2)O_(2)-Induced Cardiomyocyte Injury Medi⁃ated by AMPK/Nrf2 Pathway

作　　者：崔栋然 范方雪 武琼 王瑞[1] 侯俊德[1] 王志刚[1] CUI Dongran;FAN Fangxue;WU Qiong;WANG Rui;HOU Junde;WANG Zhigang(Anesthesiology Department of Handan Central Hospital,Handan,Hebei 056000;Anesthesiology Department of Handan First Hospital,Handan,Hebei 056000)

机构地区：[1]邯郸市中心医院麻醉科,河北邯郸056000 [2]邯郸市第一医院麻醉科,河北邯郸056000

出　　处：《岭南心血管病杂志》2024年第5期543-548,共6页South China Journal of Cardiovascular Diseases

基　　金：河北省医学科学研究课题(项目编号:20210040);邯郸市科学技术研究与发展计划项目(项目编号:22422083044ZC)。

摘　　要：目的探究艾司氯胺酮对过氧化氢(H_(2)O_(2))诱导H9c2心肌细胞损伤的作用及其机制。方法采用H_(2)O_(2)处理的H9c2细胞为心肌细胞毒模型,将细胞分为空白组、模型组(H_(2)O_(2)处理H9c2细胞)及艾司氯胺酮组(H_(2)O_(2)和艾司氯胺酮共同处理H9c2细胞)。处理24 h后,检测H9c2细胞增殖、凋亡,细胞内凋亡蛋白天冬氨酸蛋白水解酶(caspase)3/8/9,细胞内活性氧(reactive oxygen species,ROS)、丙二醛(malondialdehyde,MDA)、肿瘤坏死因子(tumor necrosis factor,TNF)-α、白细胞介素(interleukin,IL)-6和IL-1β的mRNA浓度,细胞内AMP依赖的蛋白激酶(AMP-dependent protein kinase,AMPK)磷酸化浓度及细胞核核因子相关因子2(nuclear factor-related factor 2,Nrf2)浓度。结果空白组、模型组、艾司氯胺酮组细胞增殖率分别为75.55%±3.39%、41.62%±5.88%、63.13%±6.06%。与空白组相比,模型组细胞增殖水平显著降低、凋亡细胞数量显著增加,而艾司氯胺酮组细胞增殖显著优于模型组、凋亡细胞数量显著少于模型组,差异有统计学意义(P<0.05)。模型组细胞内切割caspase 3/8/9蛋白,ROS,MDA及TNF-α、IL-6、IL-1β的mRNA浓度显著高于空白组,而艾司氯胺酮组细胞内切割caspase 3/8/9蛋白、ROS、MDA及TNF-α、IL-6、IL-1β的mRNA浓度显著低于模型组,差异有统计学意义(P<0.05)。进一步发现模型组细胞磷酸化AMPK及核内Nrf2浓度显著低于空白组,而艾司氯胺酮组细胞内上述指标浓度显著高于模型组,差异有统计学意义(P<0.05)。结论艾司氯胺酮能够通过抑制氧化应激改善H_(2)O_(2)诱导心肌细胞损伤,其作用机制与AMPK/Nrf2通路有关。Objectives To investigate the effect of Esketamine on hydrogen peroxide(H_(2)O_(2))-induced H9c2 cardiomyo‐cyte injury and its mechanism.Methods H9c2 cells treated with H_(2)O_(2) were used as cardiomyocyte toxicity model.The cells were divided into blank group,model group(H_(2)O_(2) treated H9c2 cells)and Esketamine group(H_(2)O_(2) and Esket‐amine treated H9c2 cells).After treatment for 24 h,the proliferation and apoptosis of H9c2 cells were detected.The mRNA expressions of intracellular apoptotic protein aspartic proteolytic enzyme caspase 3/8/9,intracellular reactive oxygen species(ROS),malondialdehyde(MDA),tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1βwere detected.Concentrations of intracellular AMP-dependent protein kinase(AMPK)phosphorylation and nuclear factor-related factor 2(Nrf2)were also detected.Results The cell proliferation rates of blank group,model group and Esket‐amine group were 75.55%±3.39%,41.62%±5.88%and 63.13%±6.06%,respectively.Compared with blank group,the cell proliferation level of model group was significantly decreased,and the number of apoptotic cells was significantly increased,while the cell proliferation of Esketamine group was significantly better than that of model group,and the number of apoptotic cells was significantly less than that of model group(P<0.05).The concentrations of cleaved caspase 3/8/9 protein,ROS,MDA and the mRNA expressions of TNF-α,IL-6,IL-1βin model group were significantly higher than those in blank group,while the concentrations of cleaved caspase 3/8/9 protein,ROS,MDA and the mRNA expres‐sions of TNF-α,IL-6 and IL-1βin Esketamine group were significantly lower than those in model group(P<0.05).It was further found that the concentrations of phosphorylated AMPK and nuclear Nrf2 in model group were significantly lower than those in blank group,while the concentrations of the above indexes in Esketamine group were significantly higher than those in model group(P<0.05).Conclusions Esketamine can improve H_(2)O_(2)-induced cardiomyo

关 键 词：艾司氯胺酮 心肌细胞 损伤 氧化应激 

分 类 号：R541[医药卫生—心血管疾病]