Mechanical trauma (MT) causes myocardial injury and cardiac dysfunction. However, the underlying mechanism remains largely unclear. This study investigated the role of mitochondrial dynamics in post‐traumatic cardiac dysfunction and the protective effects of melatonin. Adult male Sprague Dawley rats were subjected to 5‐minute rotations (200 revolutions at a rate of 40 rpm) to induce MT model. Melatonin was administrated intraperitoneally 5 minute after MT. Mitochondrial morphology, myocardial injury, and cardiac function were determined in vivo. There was smaller size of mitochondria and increased number of mitochondria per μm² in the hearts after MT when the secondary myocardial injury was induced. Melatonin treatment at the dose of 30 mg/kg reduced serine 616 phosphorylation of Drp1 and inhibited mitochondrial Drp1 translocation and mitochondrial fission in the hearts of rats subjected to MT, which contributed to the reduction of myocardial injury and the improvement of cardiac function. In vitro, H9c2 cells cultured in 20% traumatic plasma (TP) for 12 hour showed enhanced mitochondrial fission, mitochondrial membrane potential (∆Ψm) loss, mitochondrial cytochrome c release, and decreased mitochondrial complex I‐IV activities. Pretreatment with melatonin (100 μmol/L) efficiently inhibited TP‐induced mitochondrial fission, ∆Ψm loss, cytochrome c release, and improved mitochondrial function. Melatonin's protective effects were attributed to its role in suppressing plasma TNF‐α overproduction, which was responsible for Drp1‐mediated mitochondrial fission. Taken together, our results demonstrate for the first time that abnormal mitochondrial dynamics is involved in post‐traumatic cardiac dysfunction. Melatonin has significant pharmacological potential in protecting against MT‐induced cardiac dysfunction by preventing excessive mitochondrial fission.

中文翻译：

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动力蛋白相关蛋白1介导的线粒体裂变导致大鼠创伤后心脏功能障碍和褪黑激素的保护作用

机械创伤（MT）会导致心肌损伤和心脏功能障碍。但是，基本机制仍不清楚。这项研究调查了线粒体动力学在创伤后心脏功能障碍中的作用以及褪黑激素的保护作用。成年雄性Sprague Dawley大鼠进行5分钟旋转（200转，以40 rpm的速度）以诱发MT模型。MT后5分钟腹膜内施用褪黑激素。体内确定了线粒体形态，心肌损伤和心功能。有线粒体的更小的尺寸和每微米增加线粒体的数量²继发于继发性心肌损伤的MT后心脏中。褪黑素剂量为30 mg / kg可以降低MT大鼠的心脏中Drp1的丝氨酸616磷酸化，并抑制其线粒体Drp1易位和线粒体裂变，从而有助于减少心肌损伤和改善心功能。在体外，在20％的创伤血浆（TP）中培养12小时的H9c2细胞显示出增强的线粒体裂变，线粒体膜电位（∆m）损失，线粒体细胞色素c释放以及线粒体复合物I-IV活性降低。褪黑素（100μmol/ L）预处理可有效抑制TP诱导的线粒体裂变，ΔΨm丢失，细胞色素c释放，并改善线粒体功能。褪黑素的保护作用归因于其抑制血浆TNF-α过度生产的作用，这是Drp1介导的线粒体裂变的原因。综上所述，我们的结果首次证明了异常的线粒体动力学与创伤后心脏功能障碍有关。褪黑素通过防止线粒体过度裂变，在预防MT引起的心脏功能障碍方面具有重要的药理潜力。