右美托咪定减轻模型大鼠心肌缺血/再灌注损伤

doi:10.16352/j.issn.1001-6325.2025.03.0303

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (3): 303-309.doi: 10.16352/j.issn.1001-6325.2025.03.0303

右美托咪定减轻模型大鼠心肌缺血/再灌注损伤

刘根凤¹, 南璐², 高琴², 陈祎轩², 张静², 余鹏², 余树春^2*

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

收稿日期:2024-04-19 修回日期:2024-10-31 发布日期:2025-02-25
通讯作者: ^*ncuysc@163.com
基金资助:
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)

Dexmedetomidine alleviatesmyocardial ischemia-reperfusion injury in rat models

LIU Genfeng¹, NAN Lu², GAO Qin², CHEN Yixuan², ZHANG Jing², YU Peng², YU Shuchun^2*

1. Department of Anesthesiology, Xingguo Hospital, Gannan Medical University, Ganzhou 342400;
2. Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China

Received:2024-04-19 Revised:2024-10-31 Published:2025-02-25

摘要/Abstract

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)。

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

Abstract: 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 by1% 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.

Key words: dexmedetomidine, cuproptosis, myocardial ischemia-reperfusion injury(MI/RI), oxidative stress, inflammation

中图分类号:

R310.99

刘根凤, 南璐, 高琴, 陈祎轩, 张静, 余鹏, 余树春. 右美托咪定减轻模型大鼠心肌缺血/再灌注损伤[J]. 基础医学与临床, 2025, 45(3): 303-309.

LIU Genfeng, NAN Lu, GAO Qin, CHEN Yixuan, ZHANG Jing, YU Peng, YU Shuchun. Dexmedetomidine alleviatesmyocardial ischemia-reperfusion injury in rat models[J]. Basic & Clinical Medicine, 2025, 45(3): 303-309.

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右美托咪定减轻模型大鼠心肌缺血/再灌注损伤

Dexmedetomidine alleviatesmyocardial ischemia-reperfusion injury in rat models

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