Department of Cardiovascular Medicine, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, 29 Bulan Road, Shenzhen, Guangdong Province, China.
Department of Cardiovascular Surgery, Xijing Hospital, The Airforce Military Medical University, 127 Changle West Road, Xi'an, China.
Cell Mol Biol Lett. 2023 Apr 26;28(1):35. doi: 10.1186/s11658-022-00415-8.
Heart failure is a common complication of sepsis with a high mortality rate. It has been reported that melatonin can attenuate septic injury due to various properties. On the basis of previous reports, this study will further explore the effects and mechanisms of melatonin pretreatment, posttreatment, and combination with antibiotics in the treatment of sepsis and septic myocardial injury.
Our results showed that melatonin pretreatment showed an obvious protective effect on sepsis and septic myocardial injury, which was related to the attenuation of inflammation and oxidative stress, the improvement of mitochondrial function, the regulation of endoplasmic reticulum stress (ERS), and the activation of the AMPK signaling pathway. In particular, AMPK serves as a key effector for melatonin-initiated myocardial benefits. In addition, melatonin posttreatment also had a certain degree of protection, while its effect was not as remarkable as that of pretreatment. The combination of melatonin and classical antibiotics had a slight but limited effect. RNA-seq detection clarified the cardioprotective mechanism of melatonin.
Altogether, this study provides a theoretical basis for the application strategy and combination of melatonin in septic myocardial injury.
心力衰竭是脓毒症的常见并发症,死亡率很高。有报道称,褪黑素由于具有多种特性,可减轻脓毒症损伤。基于以往的报道,本研究将进一步探讨褪黑素预处理、后处理以及与抗生素联合治疗脓毒症和脓毒性心肌损伤的作用和机制。
我们的结果表明,褪黑素预处理对脓毒症和脓毒性心肌损伤具有明显的保护作用,这与减轻炎症和氧化应激、改善线粒体功能、调节内质网应激(ERS)以及激活 AMPK 信号通路有关。特别是,AMPK 作为褪黑素引发心肌获益的关键效应物。此外,褪黑素后处理也有一定程度的保护作用,但其效果不如预处理显著。褪黑素与经典抗生素的联合作用略有但有限。RNA-seq 检测阐明了褪黑素的心脏保护机制。
总之,本研究为褪黑素在脓毒性心肌损伤中的应用策略和联合应用提供了理论依据。