摘要： 目的 探究MCC950对心肌梗死（MI）大鼠心肌氧化应激和线粒体功能障碍的作用及其机制。方法 将30只SD大鼠随机分成假手术组、MI组和MMC950组，每组10只。通过结扎冠状动脉前降支建立MI模型。超声心动图检查大鼠心功能，HE染色观察大鼠心肌组织病理形态表现，荧光探针法检测大鼠心肌组织活性氧（ROS），ELISA检测大鼠心肌组织中氧化应激因子水平，Western blotting检测大鼠心肌组织核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎症小体及线粒体分裂、融合和生物发生相关蛋白表达。结果 MCC950改善大鼠心功能和心肌组织病理损伤，降低大鼠心肌组织ROS水平、丙二醛含量、凋亡相关斑点样蛋白斑点形成数及NLRP3、pro-caspase-1、cleaved caspase-1、pro-IL-1β、pro-IL-18、GSDMD-N、Drp1和Fis1蛋白表达水平，增加心肌组织超氧化物歧化酶含量及OPA1、Mfn2、PGC-1α和TFAM蛋白表达水平。结论 MCC950可改善MI大鼠心功能，抑制心肌氧化应激，促进心肌线粒体融合和生物发生，抑制线粒体分裂，其机制可能与其抑制NLRP3炎症小体激活有关。

MCC950对心肌梗死大鼠心功能的保护作用及其机制

王禹婷, 石菲菲, 张迪, 马淑梅

中国医科大学附属盛京医院心功能科, 沈阳 110004

收稿日期:2022-05-23发布日期:2022-11-09
通讯作者:马淑梅E-mail:masm@sj-hospital.org
作者简介:王禹婷（1990-），女，医师，硕士.
基金资助:辽宁省自然科学基金（2019-MS-10）


关键词: 核苷酸结合寡聚化结构域样受体蛋白3炎症小体, 心肌梗死, MCC950, 线粒体功能障碍, 氧化应激
Abstract: Objective To explore the effects and underlying mechanisms of MCC950 on myocardial oxidative stress and mitochondrial dysfunction in rats with myocardial infarction（MI）.Methods Thirty SD rats were randomly divided into sham，MI，and MMC950 groups （n = 10 per group）. The MI model was established through ligation of the anterior descending coronary artery. Ultrasound cardiography was performed to examine rat cardiac function. Hematoxylin and eosin staining staining was performed to observe the pathological manifestations of rat myocardial tissues. Fluorescent probe method was performed to detect reactive oxygen species（ROS）in rat myocardial tissue. ELISA was performed to identify oxidative stress factors in rat myocardial tissues. Western blotting was performed to measure the expression of nucleotide-binding oligomerization domain-like receptor protein 3（NLRP3）inflammasome and mitochondrial fission，fusion，and biogenesis-related proteins in rat myocardial tissues.Results MCC950 improved cardiac function and damaged myocardial tissues in rats； reduced ROS levels，malondialdehyde content，ASC speck formation number，and the expression levels of NLRP3，pro-caspase-1， cleaved caspase-1，pro-IL-1β ，pro-IL-18，GSDMD-N，Drp1，and Fis1 proteins； and increased super oxide dismutase content in rat myocardial tissue and the expression levels of OPA1，Mfn2，PGC-1α，and TFAM proteins. Conclusion MCC950 can improve cardiac function in MI rats，inhibit myocardial oxidative stress，promote myocardial mitochondrial fusion and biogenesis，and inhibit mitochondrial fission. The underlying mechanisms are possibly related to the inhibition of NLRP3 inflammasome activation.
Key words: nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome, myocardial infarction, MCC950, mitochondrial dysfunction, oxidative stress
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