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目的:探讨辛伐他汀对缺氧/复氧诱导的心肌细胞损伤的拮抗作用及潜在机制。方法:分离培养Sprague-Dawley(SD)大鼠(乳鼠)心肌细胞,随机分为对照组、缺氧2 h/复氧4 h(H/R4h)组、不同浓度(0.1、1.0及10μmol/L)的辛伐他汀干预组及Toll样受体4(TLR4)中和性抗体MTS510组(浓度为10μg/L)。H/R4h组给予缺氧2 h后,随即复氧4 h。细胞处理后,进行PI-AnnexinV染色用流式细胞仪检测心肌细胞的凋亡率,用ELISA法检测心肌乳酸脱氢酶(LDH)的活性;用免疫印迹法测TLR4蛋白的含量。结果:与H/R4h组相比,辛伐他汀干预组可显著降低心肌细胞的凋亡率(16.0%vs.28.6%,P<0.01)及LDH的活性(P<0.01),并呈剂量依赖性。中浓度的辛伐他汀组开始出现拮抗作用,峰值出现在高浓度辛伐他汀组,加入MTS510阻断剂可降低心肌细胞的凋亡率及LDH的活性(P<0.01)。结论:辛伐他汀对H/R造成的心肌细胞损伤具有拮抗作用,并呈剂量依赖性,其作用机制可能与TLR4信号通路有关。
Objective: To investigate the antagonistic effect and potential mechanism of simvastatin on cardiomyocyte injury induced by hypoxia / reoxygenation. Methods: Myocardial cells of Sprague-Dawley (SD) rats were isolated and cultured and randomly divided into control group, hypoxia 2 h / reoxygenation 4 h (H / R4h) group and different concentrations of 0.1, 1.0 and 10 μmol / L) simvastatin intervention group and Toll-like receptor 4 (TLR4) neutralizing antibody MTS510 group (concentration 10μg / L). H / R4h group given hypoxia 2 h, then reoxygenated 4 h. After the cells were treated, PI-AnnexinV staining was used to detect the apoptosis rate of cardiomyocytes. The activity of myocardial lactate dehydrogenase (LDH) was detected by ELISA. The content of TLR4 protein was detected by immunoblotting. RESULTS: Compared with H / R4h group, the simvastatin treatment group significantly decreased the apoptosis rate of cardiomyocytes (16.0% vs.28.6%, P <0.01) and LDH activity (P <0.01) Sex. The moderate concentration of simvastatin group began to appear antagonism, the peak appears in the high concentration of simvastatin group, adding MTS510 blockers can reduce the rate of myocardial apoptosis and LDH activity (P <0.01). Conclusion: Simvastatin has an antagonistic effect on H / R-induced cardiomyocyte injury in a dose-dependent manner, and its mechanism may be related to the TLR4 signaling pathway.