右美托咪定减轻模型大鼠心肌缺血/再灌注损伤  

Dexmedetomidine alleviates myocardial ischemia-reperfusion injury in rat models

作　　者：刘根凤 南璐 高琴 陈祎轩 张静[2] 余鹏[2] 余树春[2] LIU Genfeng;NAN Lu;GAO Qin;CHEN Yixuan;ZHANG Jing;YU Peng;YU Shuchun(Department of Anesthesiology,Xingguo Hospital,Gannan Medical University,Ganzhou 342400;Department of Anesthesiology,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,China)

机构地区：[1]赣南医科大学附属兴国医院麻醉科,江西赣州342400 [2]南昌大学第二附属医院麻醉科,江西南昌330006

出　　处：《基础医学与临床》2025年第3期303-309,共7页Basic and Clinical Medicine

基　　金：国家自然科学基金地区科学基金(82160371);赣鄱俊才支持计划·青年科技人才托举项目(2023QT05)。

摘　　要：目的探讨右美托咪定(Dex)对大鼠心肌缺血/再灌注(I/R)损伤的保护及铜死亡在其中的作用机制。方法构建Langendorff模型(I/R组),将大鼠分为:假手术组、I/R+Veh组、I/R+Dex组和I/R+Dex+ES-Cu组。连续监测缺血前即刻(T0)、再灌注(T1)、60(T2)、90 min(T3)和2 h(T4)的左室峰压(LVSP)、左室舒张末压(LVEDP)、心率(HR)、左室压力升高最大速率(+dp/dtmax)与左室压力降低最大速率(-dp/dtmax)。后用1%氯化三苯基四氮唑(TTC)染色显示心肌梗死范围,天狼星红染色评估心肌纤维化程度;ELISA测心肌酶谱、氧化应激和炎性反应;铜离子试剂盒测心肌组织中铜离子含量;Western blot检测ATF3、SPI1和FDX1蛋白表达。结果与假手术组比较,I/R组心肌梗死范围和纤维化程度增大(P<0.05),血清MDA、IL-6、IL-1β和TNF-α水平升高(P<0.05),SOD和GSH-Px活性降低(P<0.05),Dex组能显著缓解I/R组以上变化,与Dex组比较,Dex+ES-Cu组再灌注末心肌组织铜离子含量升高(P<0.05),ATF3和SPI1蛋白水平均升高,FDX1蛋白水平降低(P<0.05)。结论Dex能调节铜代谢,改善氧化应激反应和炎性反应引起的大鼠心肌缺血/再灌注损伤(MI/RI)。Objective To investigate the relationship between the protective mechanism of dexmedetomidine(Dex)against myocardial ischemia-reperfusion(I/R)injury and cuproptosis.Methods The Langendorff models were constructed using SD rats(I/R group),which were divided into 4 groups according to different interventions during reperfusion as:sham group,I/R group,Dex group and Dex+ES-Cu group.The left ventricular peak pressure(LVSP)of the rats in the above four groups were continuously monitored in the immediate pre-ischemic period(T0),30 min of reperfusion(T1),60 min reperfusion(T2),90 min reperfusion(T3),2 h of reperfusion(T4).Left ventricular end-diastolic pressure(LVEDP),heart rate(HR),maximum rate of rise of left ventricular pressure(+dp/dtmax)and maximum rate of drop.Subsequently,the extent of myocardial infarction was shown by 1% triphenyltetrazoliumchloride(TTC)staining,and the degree of myocardial fibrosis was assessed by Sirius red staining;Myocardial enzyme profiles,oxidative stress and inflammation indexes were detected by ELISA;Copper ions were detected by copper ion detection kit in myocardial tissues;ATF3,SPI1 and FDX1 protein level expression was detected by Western blot.Results Compared with the sham-operated group,the extent of myocardial infarction and fibrosis increased in the I/R group(P<0.05),the level of serum MDA,IL-6,IL-1β,and TNF-α was elevated(P<0.05),and the activity of SOD and GSH-Px decreased(P<0.05).The Dex group significantly alleviated the above changes in the I/R group,and compared with the Dex group,in the Dex+ES-Cu group myocardial tissue copper ion content at the end of perfusion was increased(P<0.05).Both ATF3 and SPI1 protein were increased and FDX1 protein was decreased(P<0.05).Conclusions Dex can regulate copper metabolism and improve myocardial ischemia-reperfusion injury(MI/RI)resulted from oxidative stress and inflammation in rat model.

关 键 词：右美托咪定 铜死亡 心肌缺血/再灌注损伤(MI/RI) 氧化应激反应 炎性反应 

分 类 号：R310.99[医药卫生—基础医学]