Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi 710032, China.
Sci Rep. 2016 Sep 7;6:32199. doi: 10.1038/srep32199.
Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling.
急性肾损伤（AKI）是严重烧伤后的常见并发症。有报道称，褪黑素通过增加沉默信息调节因子 1（SIRT1）的表达来保护多个器官免受损伤，SIRT1 调节应激反应、炎症、细胞衰老和细胞凋亡。本研究旨在探讨褪黑素对烧伤大鼠肾脏组织的保护作用及其涉及的 SIRT1 作用机制。建立大鼠严重烧伤模型，给予或不给予褪黑素和 SIRT1 抑制剂。测定肾功能和组织学表现，以评估肾损伤的严重程度。分析乙酰化-p53（Ac-p53）、乙酰化-p65（Ac-p65）、NF-κB、乙酰化叉头框 O1（Ac-FoxO1）、Bcl-2 和 Bax 的水平，以研究潜在机制。结果表明，严重烧伤可诱导急性肾损伤，而褪黑素可部分逆转。褪黑素减轻氧化应激、炎症和细胞凋亡，同时增加 SIRT1 的表达。SIRT1 抑制可消除褪黑素的保护作用。综上所述，我们证明褪黑素通过激活 SIRT1 信号通路改善严重烧伤诱导的 AKI。
