SIRT1 activation by pterostilbene attenuates the skeletal muscle oxidative stress injury and mitochondrial dysfunction induced by ischemia reperfusion injury
SIRT1 activation by pterostilbene attenuates the skeletal muscle oxidative stress injury and mitochondrial dysfunction induced by ischemia reperfusion injury
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紫檀芪激活 SIRT1 可减轻缺血再灌注损伤引起的骨骼肌氧化应激损伤和线粒体功能障碍
DOI：
10.1007/s10495-016-1258-x
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发表时间：
2016-08-01
期刊：
影响因子：
7.2
通讯作者：
Yang, Yang
中科院分区：
文献类型：
--
作者：
Cheng, Yedong;Di, Shouyin;Yang, Yang
缺血再灌注（IR）损伤对骨骼肌有害并导致线粒体氧化应激。紫檀芪 (PTE) 是白藜芦醇的类似物，具有对抗氧化应激的有机保护作用。然而，尚无研究调查 PTE 是否可以预防 IR 相关的骨骼肌损伤。在本研究中，我们试图评估 PTE 对 IR 相关骨骼肌损伤的保护作用，并确定该过程的机制。雄性 Sprague-Dawley 大鼠接受 PTE 预处理一周，然后进行肢体 IR 手术。 IR损伤引起节段性坏死和细胞凋亡、肌丝崩解、间质增厚和炎症细胞浸润。此外，IR后肌肉组织中线粒体呼吸链活性受到抑制，甲烷二醛浓度和髓过氧化物酶活性上调，超氧化物歧化酶下调。然而，PTE 以剂量依赖性方式显着抑制这些作用。 IR损伤的机制归因于沉默信息调节因子1 (SIRT1)-FOXO1/p53通路的下调以及Bax/Bcl2比率、Cleaved聚ADP-核糖聚合酶1、Cleaved Caspase 3的增加，这些可通过PTE逆转。此外，EX527（一种 SIRT1 抑制剂）可以抵消 PTE 对 IR 相关肌肉损伤的保护作用。总之，PTE 具有针对骨骼肌红外线损伤的保护作用。这种保护作用的机制取决于SIRT1-FOXO1/p53信号通路的激活和骨骼肌细胞凋亡比例的降低。
Ischemia reperfusion (IR) injury is harmful to skeletal muscles and causes mitochondrial oxidative stress. Pterostilbene (PTE), an analogue of resveratrol, has organic protective effects against oxidative stress. However, no studies have investigated whether PTE can protect against IR-related skeletal muscular injury. In this study, we sought to evaluate the protective effect of PTE against IR-related skeletal muscle injury and to determine the mechanisms in this process. Male Sprague–Dawley rats were pretreated with PTE for a week and then underwent limb IR surgery. The IR injury induced segmental necrosis and apoptosis, myofilament disintegration, thicker interstitial spaces, and inflammatory cell infiltration. Furthermore, mitochondrial respiratory chain activity in the muscular tissue was inhibited, methane dicarboxylic aldehyde concentration and myeloperoxidase activity were up-regulated, and superoxide dismutase was down-regulated after IR. However, these effects were significantly inhibited by PTE in a dose-dependent manner. The mechanism underlying IR injury is attributed to the down-regulation of silent information regulator 1 (SIRT1)-FOXO1/p53 pathway and the increase of the Bax/Bcl2 ratio, Cleaved poly ADP-ribose polymerase 1, Cleaved Caspase 3, which can be reversed with PTE. Furthermore, EX527, an SIRT1 inhibitor, counteracted the protective effects of PTE on IR-related muscle injury. In conclusion, PTE has protective properties against IR injury of the skeletal muscles. The mechanism of this protective effect depends on the activation of the SIRT1-FOXO1/p53 signaling pathway and the decrease of the apoptotic ratio in skeletal muscle cells.