Dexmedetomidine attenuates hypoxia/reoxygenation injury in primary neonatal rat cardiomyocytes.
Dexmedetomidine attenuates hypoxia/reoxygenation injury in primary neonatal rat cardiomyocytes.
复制标题
右美托咪定减轻原代新生大鼠心肌细胞缺氧/复氧损伤
DOI：
10.3892/etm.2017.4537
复制
发表时间：
2017-07
影响因子：
2.7
通讯作者：
Ji FH
中科院分区：
文献类型：
--
作者：
Peng K;Qiu Y;Li J;Zhang ZC;Ji FH
右美托咪定的全身给药可提供针对缺血/再灌注（I/R）损伤的心脏保护;然而，右美托咪定对心肌细胞的直接影响尚未阐明。本研究探讨了右美托咪定对缺氧/复氧（H/R）条件下原代乳鼠心肌细胞的影响。为了模拟体内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，随后再氧合24小时。还检查了缺氧前2 h右美托咪定预处理和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响应曲线来分析细胞活力和活性。一个特殊的缩放指数，定义为归一化细胞指数（NCI），用于尽量减少实验间变异的影响。根据NCI的时程曲线下面积值生成剂量-效应曲线。H/R暴露显著降低细胞活力和活性。此外，细胞毒性与右美托咪定的临床相关浓度无关。右美托咪定预处理浓度依赖性地改善了H/R损伤后心肌细胞NCI的降低。此外，在3至200 nM的浓度下，右美托咪定后处理改善了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乳鼠心肌细胞的H/R损伤。
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 in vivo 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.