Targeting Smox Is Neuroprotective and Ameliorates Brain Inflammation in Cerebral Ischemia/Reperfusion Rats
Targeting Smox Is Neuroprotective and Ameliorates Brain Inflammation in Cerebral Ischemia/Reperfusion Rats
复制标题
靶向 Smox 对脑缺血/再灌注大鼠具有神经保护作用并改善脑炎症
DOI：
10.1093/toxsci/kfy300
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发表时间：
2019-04-01
影响因子：
3.8
通讯作者：
Dai, Xiaozhen
中科院分区：
文献类型：
--
作者：
Fan, Jiawei;Chen, Mei;Dai, Xiaozhen
精胺氧化酶（Smox）是多胺氧化酶的一员，已被证明与缺血性脑损伤有关。在本研究中，我们发现在大鼠大脑中动脉闭塞（MCAO）模型和培养的原代神经元中，氧糖剥夺和再氧化（OGD/R）后，Smox的表达增加。腺相关病毒RNA干扰系统下调Smox可显著减少mcao诱导的脑梗死体积和神经功能缺损，减少神经元凋亡和炎症反应。此外，OGD/R后神经元上清处理的小胶质细胞明显活化，IL-6和TNF-α表达增加。然而，在OGD/R后，用Smox下调神经元的上清液处理的小胶质细胞中，观察到小胶质细胞的激活以及IL-6和TNF-α的表达显著降低。由此可见，Smox是脑缺血损伤的重要介质，可能成为脑缺血患者的治疗靶点。
Spermine oxidase (Smox) is a member of the polyamine oxidases and has been demonstrated to be involved in ischemic brain damage. In this study, we found that Smox expression was increased in a rat middle cerebral artery occlusion (MCAO) model and in cultured primary neurons after oxygen-glucose deprivation and reoxygenation (OGD/R). Smox downregulation by the adeno-associated virus RNA interference system significantly reduced the MCAO-induced brain infarct volume and neurological deficits and decreased neuronal apoptosis and inflammatory reactions. In addition, significant microglial activation and increased IL-6 and TNF-α expression were observed in microglia treated with supernatant from neurons after OGD/R. However, a significant reduction in microglial activation as well as IL-6 and TNF-α expression was observed in microglia treated with supernatant from Smox downregulated neurons after OGD/R. Therefore, the results indicated that Smox is an important mediator of cerebral ischemia injury and may be a therapeutic target for cerebral ischemia patients.