褪黑素对大鼠心肌缺血再灌注损伤的保护作用和新机制  

Protective effects and mechanism of melatonin on myocardial ischemia reperfusion injury in rats

作　　者：杨吉平[1] 费琳[2] 余蕾[1] 钟钰西 柴学军 YANG Ji-ping;FEI Lin;YU Lei;ZHONG Yu-xi;CHAI Xue-jun(Institute of Basic Medical Sciences,Shanxi Key Laboratory of Ischemic Cardiovascular Disease,Xi'an Medical University,Xi'an 710021;Departments of Psychiatry and Psychology,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安医学院基础医学研究所,陕西省缺血性心血管疾病重点实验室,陕西西安710021 [2]西安交通大学第一附属医院精神心理科,陕西西安710061

出　　处：《解剖科学进展》2021年第3期261-264,共4页Progress of Anatomical Sciences

基　　金：陕西省教育厅重点实验室项目(19JS061);陕西省科技厅一般项目(2021JM-492,2020JM-603);西安医学院博士科研启动基金(2018DOC05)。

摘　　要：目的观察褪黑素对大鼠心肌缺血再灌注损伤(IRI)的作用,并从细胞坏死方面探讨其可能机制。方法将48只SD大鼠随机分为4组:假手术组、模型组、褪黑素低剂量(1 mg/kg)组、褪黑素高剂量(5mg/kg)组,采用冠状动脉左前降支阻断法建立大鼠心肌梗死模型,缺血30 min后再灌注90 min,建立心肌IRI模型。用氯化三苯四唑(TTC)染色法检测心肌梗死面积,并测定左心室舒张末压(LVEDP)和左心室发展压(LVDP)以反映心脏功能。用Western blot检测受体相互作用蛋白激酶3(RIPK3)及磷酸化MLKL的表达水平。结果心肌IRI后,心梗面积较假手术组显著增加,LVEDP值升高,而LVDP值降低,损伤区RIPK3及磷酸化MLKL蛋白表达水平显著增加(P<0.01)。与IRI组相比,褪黑素可剂量依赖性地减小梗死面积,降低LVEDP值,回升LVDP值,改善心功能,并抑制RIPK3及磷酸化MLKL蛋白的表达水平。结论褪黑素对大鼠心肌IRI的保护作用与抑制程序性细胞坏死关键蛋白的表达相关。Objective To observe the protective effect of melatonin on myocardial ischemia reperfusion injury(IRI) in rats and to explore the possible mechanism of cell necrosis. Methods 48 Sprague-Dawley rats were randomly divided into sham group, model group, low-dose melatonin group(1 mg/kg) and high-dose melatonin group(5 mg/kg). Myocardial infarction model was established by blocking left anterior descending coronary artery for 30 minutes and reperfusion for 90 min. Myocardial infarction area was detected by triphenyltetrazole chloride(TTC) staining. The values left ventricular end-diastolic pressure(LVEDP) and left ventricular developmental pressure(LVDP) were measured for reflecting cardiac function. The expressions of receptor interaction protein kinase 3(RIPK3) and phosphorylation mixed lineage kinase domain-like(pMLKL) protein were detected by Western blot. Results Myocardial infarction area was significantly increased, LVEDP value increased, LVDP value decreased, and the expression level of RIPK3 and pMLKL protein in the damaged area increased significantly after myocardial IRI(P<0.01). Compared with IRI group, melatonin decreased infarct area in dose-dependent manner, decreased LVEDP value, increased LVDP value, improved cardiac function, and inhibited RIPK3 and pMLKL protein expression(P<0.05). Conclusion The protective effect of melatonin on myocardial IRI is related to inhibiting the expression of key proteins of programmed cell necrosis in rats.

关 键 词：心肌 程序性坏死 缺血再灌注损伤 褪黑素 

分 类 号：R541.7[医药卫生—心血管疾病]