Melatonin Alleviates Renal Injury in Mouse Model of Sepsis.

Melatonin Alleviates Renal Injury in Mouse Model of Sepsis.
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褪黑激素减轻脓毒症小鼠模型的肾损伤

DOI:
10.3389/fphar.2021.697643
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发表时间:
2021
影响因子:
5.6
通讯作者:
Lu Q
Lu Q
中科院分区:
医学2区
文献类型:
--
作者:
Chen L;Han Z;Shi Z;Liu C;Lu Q

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褪黑素(n -乙酰基-5-甲氧基色胺;MLT)已被证明对肾脏损伤具有肾脏保护作用。然而,MLT在脓毒症致肾损伤中的保护作用机制尚不清楚。在本研究中,在CLP(盲肠结扎穿刺)模型中,MLT通过增加BUN(血尿素氮)和SCR(血清肌酐)和减少纤维化来减轻肾功能障碍。RNA-seq分析显示,MLT对肾损伤的氧化应激有抑制作用。我们的体外研究表明,MLT通过下调HK-2细胞中的SOD2和上调Nox4来抑制lps诱导的ROS(活性氧)产生的积累。此外,我们发现MLT通过降低Il-1α、Il-1β、Mcp-1和Tgf-β1 mrna水平减轻了炎症反应。综上所述,在评价MLT对脓毒症引起的急性肾损伤的治疗效果时,结果显示MLT通过调节ROS的产生来减轻肾损伤。
Melatonin (N-acetyl-5-methoxytryptamine; MLT) has been shown to have a renal-protective effect against kidney injury. However, the mechanisms underlying the protective role of MLT in sepsis-induced renal injury are yet to be revealed. In this study, MLT alleviated renal dysfunction with the increase of BUN (blood urea nitrogen) and SCR (serum creatinine) and reduction of fibrosis in the CLP (cecal ligation puncture) model. RNA-seq analysis showed that MLT repressed the oxidant stress in response to kidney injury. Our in vitro study showed that MLT suppresses LPS-induced accumulation of ROS (reactive oxygen species) production via SOD2 downregulation and Nox4 upregulation in HK-2 cells. Furthermore, we found that MLT alleviated the inflammatory response, with the mRNA-level reduction of Il-1α, Il-1β, Mcp-1, and Tgf-β1. Taken together, in evaluating the therapeutic effect of MLT on sepsis-induced acute kidney injury, the results showed that MLT alleviated renal damage by regulating the production of ROS.
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