AIM:To investigate whether melatonin can ameliorate acute myocardial infarction(AMI)by in⁃hibiting ferroptosis.METHODS:H9C2 cells were cultured in AnaeroPack system with low sugar and serum-free medium for 10 h to con...AIM:To investigate whether melatonin can ameliorate acute myocardial infarction(AMI)by in⁃hibiting ferroptosis.METHODS:H9C2 cells were cultured in AnaeroPack system with low sugar and serum-free medium for 10 h to construct a cell model of AMI.Then cells were treated with melatonin and ferroptosis inducer erastin.The cell activity,reactive oxygen species(ROS),lipid peroxidation,mitochondrial membrane potential(MMP),and ferroptosis related protein expression were detected.A rat model of AMI induced by isoprenaline(ISO)injection was established to evaluate the effects of melatonin,in which the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,iron ion and ferroptosis related protein expression were examined.RESULTS:Melatonin decreased the oxidative stress,lipid peroxidation and expression of ferroptosis protein in cardiomyocytes induced by hypoxia,but these effects could be impeded by the ferroptosis inducer erastin.Furthermore,in vivo experiments,we also found that melatonin im⁃proved the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,and alleviated iron ion accu⁃mulation and ferroptosis.CONCLUSION:The cardioprotective effects of melatonin in AMI are associated with the inhi⁃bition of ferroptosis.展开更多
基金Supported by Guangdong Medical Research Foundation(No.A2024382)Guangdong Provincial Bureau of Traditional Chinese Medicine research project(No.20231321)Scientific Research Start Plan of Shunde Hospital,Southern Medical University(No.SRSP2022012,No.SRSP2022016)。
文摘AIM:To investigate whether melatonin can ameliorate acute myocardial infarction(AMI)by in⁃hibiting ferroptosis.METHODS:H9C2 cells were cultured in AnaeroPack system with low sugar and serum-free medium for 10 h to construct a cell model of AMI.Then cells were treated with melatonin and ferroptosis inducer erastin.The cell activity,reactive oxygen species(ROS),lipid peroxidation,mitochondrial membrane potential(MMP),and ferroptosis related protein expression were detected.A rat model of AMI induced by isoprenaline(ISO)injection was established to evaluate the effects of melatonin,in which the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,iron ion and ferroptosis related protein expression were examined.RESULTS:Melatonin decreased the oxidative stress,lipid peroxidation and expression of ferroptosis protein in cardiomyocytes induced by hypoxia,but these effects could be impeded by the ferroptosis inducer erastin.Furthermore,in vivo experiments,we also found that melatonin im⁃proved the myocardial infarction size,cardiac injury,pathological changes,oxidative stress,and alleviated iron ion accu⁃mulation and ferroptosis.CONCLUSION:The cardioprotective effects of melatonin in AMI are associated with the inhi⁃bition of ferroptosis.
文摘旨在研究Nrf2/HO-1通路在日本脑炎病毒(Japanese encephalitis virus, JEV)感染引起神经细胞损伤中的作用机制,本试验建立Nrf2激动剂叔丁基对苯二酚(tert-butylhydroquinone, TBHQ)处理JEV感染的小鼠神经瘤母N2a细胞的体外感染模型。N2a细胞四种处理分别为空白DMEM对照组(Control)、JEV感染组(JEV)、TBHQ处理组(TBHQ)、JEV感染+TBHQ处理组(JEV+TBHQ)。不同处理后观察细胞病变,检测ROS水平及MDA、SOD、CAT含量变化,利用qPCR和WB技术检测Nrf2、HO-1的mRNA和蛋白的表达,并通过免疫荧光法检测各组细胞Nrf2蛋白表达情况,以及炎性因子及病毒含量。结果显示,JEV感染N2a细胞后随着时间延长ROS水平逐渐升高,且在36 h ROS水平最高。JEV感染后36 h Nrf2、HO-1的mRNA均升高,炎性因子水平升高。JEV感染N2a细胞后细胞皱缩,胞膜破裂,ROS、MDA水平升高,SOD、CAT水平降低;用40μmol·L^(-1)TBHQ处理6 h后减轻了细胞损伤,降低了ROS、MDA水平,提高了SOD、CAT活性。JEV和TBHQ均激活了Nrf2、HO-1的mRNA和蛋白的表达,用JEV+TBHQ联合处理Nrf2/HO-1通路的相关蛋白表达水平明显升高,且免疫荧光法检测细胞内Nrf2入核现象明显,且TNF-α、IL-6的mRNA水平及病毒的含量下降。上述结果表明,TBHQ能够通过Nrf2/HO-1通路减轻JEV引起的细胞氧化应激及炎症水平。
