The Involvement of Mitochondrial Biogenesis in Selenium Reduced Hyperglycemia-Aggravated Cerebral Ischemia Injury
The Involvement of Mitochondrial Biogenesis in Selenium Reduced Hyperglycemia-Aggravated Cerebral Ischemia Injury
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DOI：
10.1007/s11064-020-03055-6
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发表时间：
2020-05
影响因子：
4.4
通讯作者：
Lan Yang;Yan-mei Ma
中科院分区：
文献类型：
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作者：
Lan Yang;Yan-mei Ma
硒已被证明具有抗氧化和神经保护作用，通过调节线粒体功能和激活线粒体生物合成。我们以前的研究也表明，硒通过调节线粒体的分裂和融合来保护神经元免受谷氨酸毒性和高血糖诱导的损伤。然而，线粒体生物合成是否参与硒减轻高血糖加重的脑缺血再灌注（I/R）损伤尚不清楚。本研究的目的是确定硒是否通过促进线粒体生物合成来保护神经元免受高血糖加重的脑I/R损伤。体外缺氧加高糖模型降低了细胞活力，增加了活性氧的产生，同时刺激了线粒体生物合成信号。硒预处理显著降低了细胞死亡，并进一步激活了线粒体生物合成信号。在体实验中，高血糖状态下大脑中动脉缺血30 min再灌注24 h后，与正常血糖缺血大鼠相比，神经功能缺损加重，梗死体积增大，神经元损伤和氧化应激加重。与体外结果一致，硒治疗减轻了高血糖缺血性动物的缺血性损伤。硒还能减轻高血糖缺血引起的线粒体结构变化，进一步促进线粒体生物合成信号转导。硒激活线粒体生物合成信号通路，保护线粒体结构完整性，改善高血糖大鼠脑I/R损伤。
Selenium has been shown to possess antioxidant and neuroprotective effects by modulating mitochondrial function and activating mitochondrial biogenesis. Our previous study has also suggested that selenium protected neurons against glutamate toxicity and hyperglycemia-induced damage by regulating mitochondrial fission and fusion. However, it is still not known whether the mitochondrial biogenesis is involved in selenium alleviating hyperglycemia-aggravated cerebral ischemia reperfusion (I/R) injury. The object of this study is to define whether selenium protects neurons against hyperglycemia-aggravated cerebral I/R injury by promoting mitochondrial biogenesis. In vitro oxygen deprivation plus high glucose model decreased cell viability, enhanced reactive oxygen species production, and meanwhile stimulated mitochondrial biogenesis signaling. Pretreated with selenium significantly decreased cell death and further activated the mitochondrial biogenesis signaling. In vivo 30 min of middle cerebral artery occlusion in the rats under hyperglycemic condition enhanced neurological deficits, enlarged infarct volume, exacerbated neuronal damage and oxidative stress compared with normoglycemic ischemic rats after 24 h reperfusion. Consistent to the in vitro results, selenium treatment alleviated ischemic damage in hyperglycemic ischemic animals. Furthermore, selenium reduced the structural changes of mitochondria caused by hyperglycemic ischemia and further promoted the mitochondrial biogenesis signaling. Selenium activates mitochondrial biogenesis signaling, protects mitochondrial structure integrity and ameliorates cerebral I/R injury in hyperglycemic rats.