Bone marrow mesenchymal stem cell transplantation exerts neuroprotective effects following cerebral ischemia/reperfusion injury by inhibiting autophagy via the PI3K/Akt pathway
Bone marrow mesenchymal stem cell transplantation exerts neuroprotective effects following cerebral ischemia/reperfusion injury by inhibiting autophagy via the PI3K/Akt pathway
复制标题
骨髓间充质干细胞移植通过PI3K/Akt通路抑制自噬发挥脑缺血/再灌注损伤后的神经保护作用
DOI：
10.1016/j.brainres.2018.11.018
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发表时间：
2019-03-15
期刊：
影响因子：
2.9
通讯作者：
Lu, Pengcheng
中科院分区：
文献类型：
--
作者：
He, He;Zeng, Qing;Lu, Pengcheng
虽然脑缺血本身与高残疾率相关，但再通后继发性脑缺血/再灌注（I/R）损伤与更严重的结局相关。脑I/R损伤的机制是复杂的，涉及细胞凋亡和自噬引起的神经元死亡。自噬是细胞存活的关键，在脑I/R损伤的发病机制中起重要作用。研究表明，骨髓间充质干细胞（BMSCs）移植可有效修复和重建脑组织，这种作用可能与自噬的调节有关。为了探讨这一假设，我们将骨髓间充质干细胞静脉移植到脑I/R损伤（大脑中动脉闭塞[MCAO]）的大鼠模型中。我们的结果表明，骨髓间充质干细胞移植促进脑I/R损伤大鼠的行为恢复，减少脑梗死体积，并减少凋亡细胞的数量。此外，这种作用与自噬相关蛋白微管相关蛋白1轻链3（LC 3）和Beclin-1的表达减少有关。此外，BMSCs可显著增加脑I/R损伤后p-Akt和p-mTOR的表达。当使用LY 294002阻断PI 3 K途径时，LC 3的表达也增加。综上所述，我们的研究结果表明BMSCs对脑I/R损伤的保护作用可能与其通过激活PI 3 K/Akt/mTOR信号通路抑制自噬有关。
Although cerebral ischemia itself is associated with a high rate of disability, secondary cerebral ischemia/reperfusion (I/R) injury following recanalization is associated with much more severe outcomes. The mechanisms underlying cerebral I/R injury are complex, involving neuronal death caused by apoptosis and autophagy. Autophagy is critical for cell survival and plays an important role in the pathogenesis of cerebral I/R injury. Research has indicated that transplantation of bone marrow mesenchymal stem cells (BMSCs) is effective in repairing and reconstructing brain tissue, and that this effect may be associated with the regulation of autophagy. To explore this hypothesis, we intravenously transplanted BMSCs into a rat model of cerebral I/R injury (middle cerebral artery occlusion [MCAO]). Our results indicated that BMSCs transplantation promoted behavioral recovery, reduced cerebral infarction volume, and decreased the number of apoptotic cells in rats exposed to cerebral I/R injury. Moreover, this effect was associated with reduced expression of the autophagy-associated proteins microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1. Furthermore, BMSCs remarkably increased the expression of p-Akt and p-mTOR following cerebral I/R injury. Expression of LC3 also increased when the PI3K pathway was blocked using LY294002. In summary, our results indicated that the protective effects of BMSCs in cerebral I/R injury may be associated with the inhibition of autophagy via the activation of the PI3K/Akt/mTOR signaling pathway.