Nistri Silvia, Fiorillo Claudia, Becatti Matteo, Bani Daniele
Department of Experimental & Clinical Medicine, Research Unit of Histology & Embryology, University of Florence, viale G. Pieraccini 6, 50139 Florence, Italy.
Department of, Experimental & Clinical Biomedical Sciences "Mario Serio", Section of Biochemical Sciences, University of Florence, viale G.B. Morgagni 50, 50134 Florence, Italy.
Antioxidants (Basel). 2020 Aug 21;9(9):774. doi: 10.3390/antiox9090774.
Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at relatively low, nanomolar concentrations suggests that it specifically targets a common pathogenic mechanism of HR-induced damage, namely oxidative stress. In this study we offer experimental evidence that RLX (17 nmol L-1), added to the medium of HR-exposed H9c2 rat cardiac muscle cells, significantly reduces cell oxidative damage, mitochondrial dysfunction and apoptosis. These effects appear to rely on the up-regulation of the cellular availability of reduced glutathione (GSH), a ubiquitous endogenous antioxidant metabolite. Conversely, superoxide dismutase activity was not influenced by RLX, which, however, was not endowed with chemical antioxidant properties. Taken together, these findings verify the major pharmacological role of RLX in the protection against HR-induced oxidative stress, and shed first light on its mechanisms of action.
松弛素（RLX）指的是人类天然激素松弛素-2的药物形式，已证明其能显著减少缺氧复氧（HR）诱导的组织和细胞损伤。有证据表明，RLX在相对较低的纳摩尔浓度下，对不同器官和细胞具有类似的保护作用，这表明它特异性地针对HR诱导损伤的一种常见致病机制，即氧化应激。在本研究中，我们提供了实验证据，表明添加到暴露于HR的H9c2大鼠心肌细胞培养基中的RLX（17 nmol L-1）能显著减少细胞氧化损伤、线粒体功能障碍和细胞凋亡。这些作用似乎依赖于细胞内还原型谷胱甘肽（GSH）可用性的上调，GSH是一种普遍存在的内源性抗氧化代谢物。相反，超氧化物歧化酶活性不受RLX影响，不过RLX本身不具有化学抗氧化特性。综上所述，这些发现证实了RLX在抵御HR诱导的氧化应激中的主要药理作用，并首次揭示了其作用机制。
