Previous studies have shown that propofol (PPF) plays a protective role in ischemia–reperfusion (I/R) in multiple organs and tissues. This study was aimed to explore the mechanism of PPF in ameliorating myocardial ischemia-reperfusion injury (MIRI). MIRI model was established with Sprague–Dawley rats, and PPF pretreatment was performed before reperfusion. Creatine kinase isoform (CK-MB), lactate dehydrogenase (LDH), and hematoxylin and eosin stain were used to evaluate the severity of MIRI. H9c2 cells were treated with hypoxia/reoxygenation (H/R) to simulate I/R injury in vitro. Real-time quantitative polymerase chain reaction (qPCR) was employed to assess MALAT1 and microRNA (miR)−206 expressions. Autophagy-related 3 (ATG3), LC3BⅡ/LC3BⅠ, and Beclin-1 expression were examined by western blot. Apoptosis was monitored using flow cytometry. Interaction between MALAT1 and miR-206 was determined by bioinformatics analysis, dual-luciferase reporter gene assay, RIP assay, and RNA pull-down assay. PPF pretreatment remarkably reduced CK-MB level, LDH level, myocardial infarct size, and LC3BⅡ/LC3BⅠ ratio and Beclin-1 expression in the rats with MIRI, and repressed the apoptosis of H9c2 cells exposed to H/R. PPF pretreatment markedly suppressed MALAT1 expression and enhanced miR-206 expression in both in vivo and in vitro models. MiR-206 was identified as a target of MALAT1 in cardiomyocytes, and MALAT1 could increase the expression of ATG3. Additionally, the upregulation of MALAT1 partially reversed the protective effect of PPF on cardiomyocytes in vitro. PPF modulated MALAT1/miR-206/ATG3 axis to protect cardiomyocytes against I/R injury.

中文翻译：

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丙泊酚通过调节 MALAT1/miR-206/ATG3 轴保护心肌细胞免受缺氧/复氧损伤

先前的研究表明，丙泊酚 (PPF) 在多个器官和组织的缺血再灌注 (I/R) 中起保护作用。本研究旨在探讨PPF改善心肌缺血再灌注损伤(MIRI)的机制。用Sprague-Dawley大鼠建立MIRI模型，再灌注前进行PPF预处理。肌酸激酶异构体 (CK-MB)、乳酸脱氢酶 (LDH) 和苏木精和伊红染色用于评估 MIRI 的严重程度。用缺氧/复氧 (H/R) 处理 H9c2 细胞以模拟体外 I/R 损伤。采用实时定量聚合酶链反应 (qPCR) 来评估 MALAT1 和 microRNA (miR)-206 的表达。Western blot检测自噬相关3（ATG3）、LC3BⅡ/LC3BⅠ和Beclin-1的表达。使用流式细胞术监测细胞凋亡。通过生物信息学分析、双荧光素酶报告基因分析、RIP 分析和 RNA 下拉分析确定 MALAT1 和 miR-206 之间的相互作用。PPF预处理显着降低MIRI大鼠CK-MB水平、LDH水平、心肌梗死面积、LC3BⅡ/LC3BⅠ比值和Beclin-1表达，抑制H/R暴露H9c2细胞凋亡。在体内和体外模型中，PPF 预处理显着抑制了 MALAT1 的表达并增强了 miR-206 的表达。MiR-206 被确定为心肌细胞中 MALAT1 的靶标，MALAT1 可以增加 ATG3 的表达。此外，MALAT1 的上调部分逆转了 PPF 在体外对心肌细胞的保护作用。PPF 调节 MALAT1/miR-206/ATG3 轴以保护心肌细胞免受 I/R 损伤。