Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People's Republic of China.
Department of Operating Room, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People's Republic of China.
Clin Interv Aging. 2021 Apr 15;16:621-632. doi: 10.2147/CIA.S286429. eCollection 2021.
Propofol (PPF) ameliorates ischemia/reperfusion (I/R) injury in multiple organs by reducing apoptosis and release of pro-inflammatory cytokines. This study aims to explore the mechanism of PPF in attenuating myocardial ischemia-reperfusion injury (MIRI).
Rat MIRI model was established, and PPF pre-treatment was performed 10 min before I/R. H9c2 cardiomyocytes treated with hypoxia/reoxygenation (H/R) were used to establish an in vitro model. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate HOTAIR and miR-17-5p expression levels. Flow cytometry was employed to detect the apoptosis of H9c2 cells. The interaction between HOTAIR and miR-17-5p was determined by bioinformatics analysis, luciferase reporter gene analysis, and RNA immunoprecipitation experiments. STAT3 and p-STAT3 expressions were detected by Western blot.
PPF pre-treatment significantly reduced creatine kinase isoenzyme (CK-MB) and serum lactate dehydrogenase (LDH) levels in the serum of the rats with MIRI. PPF pre-treatment remarkably up-regulated HOTAIR expression and down-regulated miR-17-5p expression in both in vivo and in vitro models. HOTAIR adsorbed miR-17-5p to repress the expression of miR-17-5p. PPF pre-treatment markedly inhibited cardiomyocyte apoptosis induced by I/R or H/R. HOTAIR knockdown could partially reverse the protective effects of PPF on MIRI. HOTAIR could activate STAT3 signaling via repressing miR-17-5p expression.
PPF protects the MIRI by modulating the HOTAIR/miR-17-5p/STAT3 axis.
丙泊酚（PPF）通过减少细胞凋亡和促炎细胞因子的释放来改善多种器官的缺血/再灌注（I/R）损伤。本研究旨在探讨 PPF 减轻心肌缺血再灌注损伤（MIRI）的机制。
建立大鼠 MIRI 模型，在 I/R 前 10 分钟进行 PPF 预处理。使用缺氧/复氧（H/R）处理的 H9c2 心肌细胞建立体外模型。采用实时定量聚合酶链反应（qRT-PCR）评估 HOTAIR 和 miR-17-5p 的表达水平。流式细胞术检测 H9c2 细胞的凋亡。通过生物信息学分析、荧光素酶报告基因分析和 RNA 免疫沉淀实验确定 HOTAIR 和 miR-17-5p 之间的相互作用。采用 Western blot 检测 STAT3 和 p-STAT3 的表达。
PPF 预处理显著降低了 MIRI 大鼠血清中的肌酸激酶同工酶（CK-MB）和血清乳酸脱氢酶（LDH）水平。PPF 预处理显著上调了体内和体外模型中 HOTAIR 的表达，下调了 miR-17-5p 的表达。HOTAIR 吸附 miR-17-5p 抑制 miR-17-5p 的表达。PPF 预处理显著抑制 I/R 或 H/R 诱导的心肌细胞凋亡。HOTAIR 敲低可部分逆转 PPF 对 MIRI 的保护作用。HOTAIR 通过抑制 miR-17-5p 的表达来激活 STAT3 信号通路。
PPF 通过调节 HOTAIR/miR-17-5p/STAT3 轴来保护 MIRI。
