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依布硒啉在急性脊髓损伤后可保护线粒体功能和氧化应激,同时抑制线粒体凋亡途径。

Ebselen protects mitochondrial function and oxidative stress while inhibiting the mitochondrial apoptosis pathway after acute spinal cord injury.

作者信息

Jia Zhi-Qiang, Li San-Qiang, Qiao Wei-Qiang, Xu Wen-Zhong, Xing Jian-Wu, Liu Jian-Tao, Song Hui, Gao Zhong-Yang, Xing Bing-Wen, He Xi-Jing

机构信息

Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xian 710004, PR China; Department of Spinal Surgery, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang 471000, PR China.

Medical College, Henan University of Science and Technology, Luoyang 471003, PR China.

出版信息

Neurosci Lett. 2018 Jun 21;678:110-117. doi: 10.1016/j.neulet.2018.05.007. Epub 2018 May 4.

Abstract

Ebselen is a fat-soluble small molecule and organic selenium compound that regulates the activity of glutathione peroxidase to alleviate mitochondrial oxidative stress and improve mitochondrial function. In the present study, we aimed to investigate the effects of ebselen on mitochondrial oxidative stress response, mitochondrial apotosis, and motor behaviors after spinal cord injury (SCI). We found that ebselen significantly increased the BBB score in motor behavior, thus suggesting a rescue effect of ebselen on motor function after SCI in rats. Meanwhile, we revealed that ebselen can increase glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities after SCI-this suggests ebselen has an antioxidant effect. Furthermore, the ATP content and Na-K-ATPase activity in mitochondria were increased by ebselen after SCI, while the mitochondrial membrane potential (MMP) was decreased by ebselen. The Cytochrome C and Smac release from mitochondria were reduced by ebselen after SCI, thus indicating improved membrane permeability by ebselen. Moreover, the alterations in caspase-3, Bax and Bcl-2 protein expression, as well as the proportion of cell apoptosis were improved by ebselen treatment, which together suggested that ebselen has an inhibitory effect on mitochondrial apotosis pathways after SCI. Taken together, our results suggest that ebselen can inhibit secondary damage caused by spinal cord injury. Indeed it plays a neuroprotective role in spinal cord injury perhaps by improving mitochondrial function and inhibiting the mitochondrial apoptosis pathway.

摘要

依布硒啉是一种脂溶性小分子有机硒化合物,它可调节谷胱甘肽过氧化物酶的活性,以减轻线粒体氧化应激并改善线粒体功能。在本研究中,我们旨在探究依布硒啉对脊髓损伤(SCI)后线粒体氧化应激反应、线粒体凋亡及运动行为的影响。我们发现,依布硒啉显著提高了运动行为中的BBB评分,这表明依布硒啉对大鼠脊髓损伤后的运动功能具有挽救作用。同时,我们发现依布硒啉可增加脊髓损伤后的谷胱甘肽(GSH)含量以及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性,这表明依布硒啉具有抗氧化作用。此外,依布硒啉可增加脊髓损伤后线粒体中的ATP含量及Na-K-ATP酶活性,而依布硒啉可降低线粒体膜电位(MMP)。依布硒啉可减少脊髓损伤后线粒体中细胞色素C和Smac的释放,从而表明依布硒啉可改善膜通透性。此外,依布硒啉处理可改善caspase-3、Bax和Bcl-2蛋白表达的变化以及细胞凋亡比例,这共同表明依布硒啉对脊髓损伤后的线粒体凋亡途径具有抑制作用。综上所述,我们的结果表明依布硒啉可抑制脊髓损伤引起的继发性损伤。实际上,它可能通过改善线粒体功能和抑制线粒体凋亡途径在脊髓损伤中发挥神经保护作用。

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