Department of Anesthesiology and SICU, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, PR China.
Department of Intensive Care Unit, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, PR China.
Rev Port Cardiol (Engl Ed). 2021 Apr;40(4):273-281. doi: 10.1016/j.repc.2020.07.019. Epub 2021 Mar 11.
Dexmedetomidine is a highly selective alpha-2 adrenoceptor agonist that has sedative and analgesic properties and myocardial protective effects. However, the mechanism underlying the protective effect of dexmedetomidine on cardiomyocytes remains unknown. This study mainly aimed to investigate the effects of dexmedetomidine on the generation of reactive oxygen species (ROS) in cardiomyocytes and whether it inhibits the apoptosis of cardiomyocytes by affecting antioxidant enzyme expression.
Neonatal rat cardiomyocytes were pretreated with dexmedetomidine (100 nM) for 24 h. The cardiomyocytes were then incubated with 200 μM hydrogen peroxide solution (HO) for 4 h. PCR assay was used to determine the mRNA expression of antioxidant enzymes. Western blot assay was used to determine the protein expression of antioxidant enzymes. Fluorescence microscopy with the MitoSOX probe was used to detect the formation of ROS in cardiomyocytes, and fluorescence-activated cell sorting with annexin V/PI was used to determine the number of apoptotic cardiomyocytes.
Dexmedetomidine reduced ROS generation and antioxidant enzymes levels in cardiomyocytes before HO stimulation (p<0.05). However, ROS generation and apoptosis in cardiomyocytes were significantly increased after HO treatment, and dexmedetomidine pretreatment markedly inhibited the changes (p<0.05).
For the first time, to the best of our knowledge, our study shows that dexmedetomidine has a protective effect on cardiomyocytes through inhibition of ROS-induced apoptosis, and more importantly, this effect is independent of antioxidant enzyme mRNA and protein expression.
右美托咪定是一种高选择性的α-2 肾上腺素受体激动剂，具有镇静和镇痛作用以及心肌保护作用。然而，右美托咪定对心肌细胞保护作用的机制尚不清楚。本研究主要旨在探讨右美托咪定对心肌细胞活性氧（ROS）生成的影响，以及通过影响抗氧化酶表达是否抑制心肌细胞凋亡。
用右美托咪定（100 nM）预处理乳鼠心肌细胞 24 h。然后，将心肌细胞用 200 μM 过氧化氢溶液（HO）孵育 4 h。聚合酶链反应（PCR）检测抗氧化酶的 mRNA 表达。蛋白质印迹法（Western blot）检测抗氧化酶的蛋白表达。用 MitoSOX 探针荧光显微镜检测心肌细胞中 ROS 的形成，用 annexin V/PI 荧光激活细胞分选术检测凋亡心肌细胞的数量。
在 HO 刺激前，右美托咪定降低了心肌细胞中 ROS 的生成和抗氧化酶水平（p<0.05）。然而，HO 处理后心肌细胞中 ROS 的生成和凋亡明显增加，右美托咪定预处理显著抑制了这些变化（p<0.05）。
据我们所知，这是首次研究表明，右美托咪定通过抑制 ROS 诱导的凋亡对心肌细胞具有保护作用，更重要的是，这种作用独立于抗氧化酶 mRNA 和蛋白表达。
