Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
Department of Intensive Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
Int J Mol Med. 2018 Apr;41(4):2328-2338. doi: 10.3892/ijmm.2018.3384. Epub 2018 Jan 12.
Dexmedetomidine is a commonly used α2-adreno-ceptor agonist, which affects various organs, including providing beneficial effects on the heart. However, the mechanism underlying the cardiac benefit remains to be fully elucidated. In the present study, it was demonstrated that dexmedetomidine pretreatment on primary cultured rat cardiomyocytes protected against reactive oxygen species (ROS)‑induced apoptosis. In terms of the potential mechanism, it was demonstrated that dexmedetomidine inhibited mitochondrial biogenesis and mitochondrial respiratory complexes, but with increased coupling efficiency. However, dexmedetomidine upregulated mitochondrial membrane potential (Δψm) and resisted against the loss of Δψm induced by carbonilcyanide p‑triflouromethoxyphenylhydrazone. Due to the importance of mitochondria affecting ROS, the present study investigated the dexmedetomidine‑suppressed mitochondrial response to H2O2 stimulation, which was explained by suppressed ROS levels and the suppression of the increased oxygen consumption rate. Results demonstrated for the first time, to the best of our knowledge, a novel protective mechanism for dexmedetomidine on cardiomyocytes through the attenuated response of mitochondria towards H2O2, which had a protective effect against ROS‑induced apoptosis.
右美托咪定是一种常用的 α2-肾上腺素能受体激动剂，它影响包括心脏在内的各种器官，具有有益的心脏作用。然而，其心脏保护作用的机制仍有待充分阐明。本研究表明，右美托咪定预处理原代培养的大鼠心肌细胞可防止活性氧（ROS）诱导的细胞凋亡。就潜在机制而言，右美托咪定抑制线粒体生物发生和线粒体呼吸复合物，但增加了偶联效率。然而，右美托咪定上调了线粒体膜电位（Δψm），并抵抗了羰基氰化物 p-三氟甲氧基苯腙诱导的Δψm 丧失。由于线粒体对 ROS 的重要性，本研究调查了右美托咪定抑制线粒体对 H2O2 刺激的反应，这可以通过抑制 ROS 水平和抑制耗氧量的增加来解释。结果首次表明，据我们所知，右美托咪定通过减轻线粒体对 H2O2 的反应，为心肌细胞提供了一种新的保护机制，对 ROS 诱导的细胞凋亡具有保护作用。
