Maresin 1 attenuates the inflammatory response and mitochondrial damage in mice with cerebral ischemia/reperfusion in a SIRT1-dependent manner
Maresin 1 attenuates the inflammatory response and mitochondrial damage in mice with cerebral ischemia/reperfusion in a SIRT1-dependent manner
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DOI：
10.1016/j.brainres.2019.01.013
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发表时间：
2019-05-15
期刊：
影响因子：
2.9
通讯作者：
Cao, Jun
中科院分区：
文献类型：
--
作者：
Xian, Wenjing;Li, Tong;Cao, Jun
Maresin 1（MaR 1）对脑缺血/再灌注（I/R）损伤具有脑保护作用。沉默信息调节因子1（SIRT 1）信号的激活也被证明可以抑制脑I/R损伤。我们推测MaR 1可能通过激活SIRT 1信号通路保护脑I/R损伤。本研究探讨了MaR 1对脑I/R损伤的保护作用，并阐明了其可能的机制。在存在或不存在MaR 1或SIRT 1抑制剂EX 527的情况下，将小鼠暴露于治疗，然后进行大脑中动脉闭塞（MCAO）手术。MaR 1通过上调SIRT 1和Bcl 2表达，下调乙酰化核因子κ B（AC-NF-κ B B）和Bax表达，降低促炎因子（IL-1、IL-6和TNF-α）水平，增加线粒体膜电位，减轻神经元变性、梗死面积和脑I/R的神经功能缺损，从而发挥脑保护作用。这些保护作用被SIRT 1抑制剂EX 527部分阻断，表明SIRT 1信号可能特异性地参与MaR 1对脑I/R损伤的保护作用。总之，我们的研究结果表明，MaR 1治疗减轻脑I/R损伤，通过减少炎症反应和线粒体损伤，通过激活SIRT 1信号。
Maresin 1(MaR1) confers brain-protective effects against cerebral ischemia/reperfusion (I/R) injury. Activation of silent information regulator 1 (SIRT1) signaling has also been demonstrated to inhibit cerebral I/R injury. We hypothesize that MaR1 may protect against cerebral I/R injury by activating SIRT1 signaling. The present study investigated the protective effect of MaR1 treatment on cerebral I/R injury and elucidated the potential mechanisms. Mice were exposed to the treatment in the presence or absence of MaR1 or the SIRT1 inhibitor EX527 and then subjected to the middle cerebral artery occlusion (MCAO) operation. MaR1 conferred a brain-protective effect by up-regulating SIRT1 and Bcl2 expression, down-regulating acetylated neuclear factor kappaB (AC-NF-kappa B) and Bax expression, reducing pro-inflammatory factor levels (IL-1, IL-6 and TNF-alpha), increasing the mitochondrial membrane potential, and diminishing neuronal degeneration, the infarct size and the neurological defects of cerebral I/R. These protective effects were partially blocked by the SIRT1 inhibitor EX527, indicating that SIRT1 signaling might be specifically involved in the protection provided by MaR1 against cerebral I/R injury. In summary, our results demonstrate that MaR1 treatment attenuates cerebral I/R injury by reducing inflammatory responses and mitochondrial damage via activation of SIRT1 signaling.