Peng Ke, Qiu Yun, Li Jian, Zhang Zhao-Cai, Ji Fu-Hai
Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Department of Anesthesiology, Suzhou Yongding Hospital, Suzhou, Jiangsu 215299, P.R. China.
Exp Ther Med. 2017 Jul;14(1):689-695. doi: 10.3892/etm.2017.4537. Epub 2017 Jun 1.
Systemic administration of dexmedetomidine provides cardioprotection against ischemia/reperfusion (I/R) injury; however, the direct effects of dexmedetomidine on cardiomyocytes have not been clarified. The present study investigated the effects of dexmedetomidine on primary neonatal rat cardiomyocytes under hypoxic/reoxygenation (H/R) conditions. In order to simulate I/R injury, primary neonatal rat cardiomyocytes were cultured under hypoxic conditions for 1 h and subsequently reoxygenated for 24 h. The effects of preconditioning with dexmedetomidine 2 h before hypoxia and postconditioning during reoxygenation were also examined. Cellular viability and activity were analyzed by monitoring the dynamic response profile of living cells using a real-time cell analyzer system. A special scaled index, defined as the normalized cell index (NCI), was used to minimize the influence of inter-experimental variations. The dose-effect curve was generated from the area under the time-course curve values of NCI. H/R exposure markedly decreased cell viability and activity. Furthermore, no cytotoxicity was associated with a clinically relevant concentration of dexmedetomidine. Preconditioning with dexmedetomidine concentration-dependently ameliorated the reductions in NCI in cardiomyocytes following H/R injury. Additionally, postconditioning with dexmedetomidine improved the reductions in NCI at concentrations between 3 and 200 nM. Finally, the effect of 3-40 nM dexmedetomidine postconditioning was greater than preconditioning. These results indicated that preconditioning and postconditioning with dexmedetomidine attenuated H/R injury in primary neonatal rat cardiomyocytes at the cellular level.
静脉注射右美托咪定可提供针对缺血/再灌注（I/R）损伤的心脏保护作用；然而，右美托咪定对心肌细胞的直接作用尚未明确。本研究调查了右美托咪定在缺氧/复氧（H/R）条件下对原代新生大鼠心肌细胞的影响。为了模拟I/R损伤，将原代新生大鼠心肌细胞在缺氧条件下培养1小时，随后复氧24小时。还检测了在缺氧前2小时用右美托咪定预处理以及在复氧期间后处理的效果。通过使用实时细胞分析仪系统监测活细胞的动态反应曲线来分析细胞活力和活性。使用一个特殊的标度指数，即归一化细胞指数（NCI），以尽量减少实验间差异的影响。剂量-效应曲线由NCI的时间进程曲线值下的面积生成。H/R暴露显著降低了细胞活力和活性。此外，临床相关浓度的右美托咪定未显示出细胞毒性。右美托咪定预处理可浓度依赖性地改善H/R损伤后心肌细胞中NCI的降低。此外，右美托咪定后处理在3至200 nM的浓度范围内改善了NCI的降低。最后，3 - 40 nM右美托咪定后处理的效果大于预处理。这些结果表明，右美托咪定预处理和后处理在细胞水平上减轻了原代新生大鼠心肌细胞的H/R损伤。
