丙泊酚对实验性心肌梗死大鼠的心肌保护作用及机制
张明晓^*, 田庆鑫, 刘建龙
温州医科大学附属第一医院麻醉科，温州 325000
摘要
本研究旨在探讨丙泊酚对实验性心肌梗死大鼠的心肌保护作用。采用结扎左冠状动脉前降支建立心肌梗死大鼠模型，模型大鼠用丙泊酚处理，用超声心动图检测心功能，用多导生物记录仪检测心脏血流动力学变化，用HE染色检测梗死心肌的病理学变化，用实时定量PCR和蛋白质印迹分析心肌肥厚标志基因和纤维化标志蛋白的表达。结果显示，与假手术组相比，模型组发生大面积(>40%)心肌梗死，心功能受损，左心室舒张末压(left ventricular end-diastolic pressure, LVEDP)显著升高。丙泊酚减轻了心肌梗死所致的心功能损害，显著降低模型组LVEDP。丙泊酚显著降低模型大鼠的肺重/体重比、心重/体重比、左心室重/体重比和左心房重/体重比。丙泊酚显著提高模型大鼠心肌舒张肌应变率，并下调心肌肥厚标志物——心房利钠肽和β-肌球蛋白重链mRNA表达水平，逆转心肌梗死引起的基质金属蛋白酶2 (matrix metalloproteinase 2, MMP2)、MMP9、基质金属蛋白酶组织抑制因子-2 (tissue inhibitor of metalloproteinase-2, TIMP-2)蛋白表达水平上调。以上结果提示，丙泊酚能够减轻心肌梗死后的不良心室重构和心功能障碍，减少心肌肥厚和纤维化，对大鼠冠状动脉结扎诱发的实验性心肌梗死具有一定的保护作用。


关键词： 丙泊酚; 心肌梗死; 心肌肥厚; 心室重构; 纤维化
分类号：R965

The myocardial protective effect of propofol on rats with experimental myocardial infarction and its mechanism
ZHANG Ming-Xiao^*, TIAN Qing-Xin, LIU Jian-Long
Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
Abstract
The aim of the present study was to investigate the protective effect of propofol on the experimental myocardial infarction in rats. The myocardial infarction model was established by ligating the anterior descending branch of left coronary artery in rats. Model rats were treated with propofol. Cardiac function was evaluated by echocardiography. Cardiac hemodynamic changes were detected by multiconductor biorecorder. Pathological changes in the infarcted myocardia were detected by HE staining. The expression levels of cardiac hypertrophy marker genes and fibrosis marker proteins were analyzed by real-time quantitative PCR and Western blot. The results showed that, compared with the sham surgery group, the model group exhibited larger infarct size (> 40%), impaired heart function, and significantly increased left ventricular end-diastolic pressure (LVEDP). Propofol reduced cardiac function impairment and decreased LVEDP in the model group. Propofol significantly reduced lung weight/body weight ratio, heart weight/body weight ratio, left ventricular weight/body weight ratio and left atrial weight/body weight ratio in the model group. Furthermore, after myocardial infarction, the administration of propofol significantly improved the diastolic strain rate, down-regulated the mRNA expression levels of myocardial hypertrophy markers, atrial natriuretic peptide and β-myosin heavy chain, and reversed the up-regulation of matrix metalloproteinase 2 (MMP2), MMP9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) induced by myocardial infarction. These results suggest propofol can reduce adverse ventricular remodeling, cardiac dysfunction, myocardial hypertrophy and fibrosis after myocardial infarction, and has protective effect against the experimental myocardial infarction induced by coronary artery ligation in rats.
Key words: propofol; myocardial infarction; cardiac hypertrophy; ventricular remodeling; fibrosis

收稿日期：2020-08-01　　录用日期：2020-10-26
通讯作者：张明晓　　E-mail: zmxmzk@126.com
引用本文：
张明晓, 田庆鑫, 刘建龙. 丙泊酚对实验性心肌梗死大鼠的心肌保护作用及机制[J]. 生理学报 2021; 73 (6): 878-884.
ZHANG Ming-Xiao, TIAN Qing-Xin, LIU Jian-Long. The myocardial protective effect of propofol on rats with experimental myocardial infarction and its mechanism. Acta Physiol Sin 2021; 73 (6): 878-884 (in Chinese with English abstract).



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