Inhibition of miR-497 improves functional outcome after ischemic stroke by enhancing neuronal autophagy in young and aged rats
Inhibition of miR-497 improves functional outcome after ischemic stroke by enhancing neuronal autophagy in young and aged rats
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DOI：
10.1016/j.neuint.2019.01.005
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发表时间：
2019-07-01
影响因子：
4.2
通讯作者：
Jin, Kunlin
中科院分区：
文献类型：
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作者：
Chen, Xudong;Lin, Siyang;Jin, Kunlin
多年来，人们发现miR-497在包括缺血性中风在内的神经系统疾病的发病机制中起着至关重要的作用。然而，其潜在机制在很大程度上仍未被探索。在这里，我们使用miR-497 agomir （miR-497激动剂），miR-497 antagomir （miR-497抑制剂）和3-MA（自噬抑制剂）治疗永久性大脑中动脉远端闭塞（dMCAO）诱导的缺血大鼠（每组n = 10-12），并在dMCAO后24小时进行功能结局评估。我们发现，miR-497安他哥米尔治疗，而不是miR-497安他哥米尔治疗，减少了缺血性卒中后的梗死面积，改善了神经功能障碍，同时上调了自噬相关蛋白LC3的表达（平均+/- SEM， p < 0.05）。而3-MA处理的缺血大鼠表现出自噬抑制，从而破坏了miR-497安他戈米尔处理组的功能恢复（p < 0.05）。有趣的是，与年轻成年缺血大鼠相比，miR-497在老年缺血大鼠功能恢复中的作用较差（p < 0.05）。我们的数据表明，抑制miR-497可以通过增强自噬来保护脑缺血损伤，并具有年龄依赖性。
Over the years miR-497 has been found to play a vital role in the pathogenesis of neurological diseases, including ischemic stroke. However, its underlying mechanism remains largely unexplored. Here, we used miR-497 agomir (miR-497 agonist), miR-497 antagomir (miR-497 inhibitor) and 3-MA (autophagy inhibitor) to treat ischemic rats (n = 10-12 per group) induced by permanent distal middle cerebral artery occlusion (dMCAO), followed the functional outcome assessment 24 h after dMCAO. We found that treatment of miR-497 antagomir, but not miR-497 angomir, reduced the infarct volume and improved neurological deficits after ischemic stroke, along with upregulation of the autophagy-related protein LC3 expression (mean +/- SEM, p < 0.05). While the ischemic rats treated with 3-MA exhibited inhibition of autophagy, which in turn abolished functional recovery as observed in miR-497 antagomir-treated group (p < 0.05). Interestingly, the role of miR-497 in functional recovery in aged ischemic rats was less effective, compared to young adult ischemic rats (p < 0.05). Our data suggest that inhibition of miR-497 could protect cerebral ischemic injury by enhancing autophagy and also age-dependent.