Department of Spinal Cord Injury and Repair, Trauma and Orthopedics, Institute of Chinese PLA, General Hospital of Jinan Military Region, Shandong, China.
Department of Neurobiology, Beijing Institute of Basic Medical Science, The Academy of Military Medical Sciences of the Chinese PLA, Guangdong, China.
J Pharm Pharmacol. 2018 Jun;70(6):760-767. doi: 10.1111/jphp.12895. Epub 2018 Feb 27.
This study aimed to investigate the cardioprotective effects of melatonin on heat stroke (HS) induced acute myocardial infarction in rats and to explore the underlying mechanisms.
Myocardial injury was induced by subjecting the anaesthetized rats to a high ambient temperature of 43°C for 70 min. Such a high ambient temperature caused hyperthermia, hypotension and myocardial injury in rats. Rats were treated with melatonin (3 mg/kg) intravenously one hour before and followed by an additional dose immediately after heat stress.
At the onset of HS, animals displayed myocardial injury evidenced by increased levels of cardiac damage indicators (e.g. total lactate dehydrogenase, cardiac troponin I and creatine kinase-MB), increased cardiac damage scores and suppressed left ventricular performance. Animals with HS also had increased cardiac oxidative stress evidenced by increased levels of lipid peroxidation (e.g. increased thiobarbituric acid reactive substances) and decreased levels of antioxidant enzymes (e.g. superoxide dismutase, catalase and reduced glutathione) and activated inflammation (e.g. increased levels of interleukin-6 and tumour necrosis factor-α). Pretreatment with melatonin significantly reversed the HS-induced myocardial injury, cardiac oxidative stress and cardiac inflammation.
Melatonin may protect against HS-induced myocardial injury in male rats by mitigating oxidative stress and inflammation.
本研究旨在探讨褪黑素对热射病(HS)诱导的大鼠急性心肌梗死的心脏保护作用,并探讨其潜在机制。
通过将麻醉大鼠置于 43°C 的高温环境中 70 分钟,诱导心肌损伤。如此高的环境温度会导致大鼠体温过高、血压降低和心肌损伤。大鼠在热应激前 1 小时静脉注射褪黑素(3mg/kg),并在热应激后立即给予额外剂量。
在 HS 发作时,动物表现出心肌损伤的迹象,包括心脏损伤标志物(如总乳酸脱氢酶、心肌肌钙蛋白 I 和肌酸激酶-MB)水平升高、心脏损伤评分升高和左心室功能降低。HS 动物还存在心脏氧化应激增加的迹象,表现为脂质过氧化水平升高(如丙二醛反应物质增加)和抗氧化酶水平降低(如超氧化物歧化酶、过氧化氢酶和还原型谷胱甘肽),以及炎症激活(如白细胞介素-6 和肿瘤坏死因子-α水平升高)。褪黑素预处理显著逆转了 HS 诱导的心肌损伤、心脏氧化应激和心脏炎症。
褪黑素通过减轻氧化应激和炎症,可能对雄性大鼠的 HS 诱导的心肌损伤具有保护作用。