L-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury
L-lysine confers neuroprotection by suppressing inflammatory response via microRNA-575/PTEN signaling after mouse intracerebral hemorrhage injury
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DOI：
10.1016/j.expneurol.2020.113214
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发表时间：
2020-05-01
影响因子：
5.3
通讯作者：
Chen, Qian-Xue
中科院分区：
文献类型：
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作者：
Cheng, Jing;Tang, Jun-Chun;Chen, Qian-Xue
赖氨酸是一种碱性氨基酸，已被证明具有神经保护作用。然而，潜在的机制仍有待阐明。在本研究中，我们研究了l -赖氨酸在体外和小鼠脑出血模型中对血红素损伤小鼠皮质神经元的神经保护作用。我们证明，l -赖氨酸治疗促进M2小胶质细胞极化，减少体外和体内炎症反应，表明l -赖氨酸可能在脑出血损伤中发挥神经保护作用。事实上，我们表明，l -赖氨酸处理可以减少体外血红蛋白损伤后皮质神经元的死亡，并减少体内脑出血后退化神经元的数量。l -赖氨酸还能改善脑出血动物在神经行为测试中的功能恢复。与PTEN在调节炎症反应中的作用一致，我们发现PTEN抑制可促进M2小胶质细胞极化，抑制小鼠ICH损伤的促炎反应，这与l -赖氨酸的神经保护作用有关。此外，我们的研究结果表明，microRNA-575直接抑制PTEN促进M2小胶质细胞极化，介导l -赖氨酸在脑出血损伤中的神经保护作用。综上所述，我们的研究结果表明，l -赖氨酸通过增强M2小胶质细胞极化和减少炎症反应，在ICH损伤后发挥神经保护作用，这一过程是由microRNA-575上调和随后的PTEN下调介导的。
L-lysine is a basic amino acid that has been shown to exert neuroprotective effect. However, the underlying mechanism remains to be elucidated. In this study, we investigate how L-lysine exerts its neuroprotective effect in hemin-insulted mouse cortical neurons in vitro and the mouse model of intracerebral hemorrhage (ICH) in vivo. We demonstrate that L-lysine treatment promotes M2 microglial polarization and reduces inflammatory response both in vitro and in vivo, suggesting that L-lysine may play a neuroprotective role in ICH injury. Indeed, we show that L-lysine treatment reduces cortical neuronal death after hemin insult in vitro and decrease the number of degenerating neurons after ICH in vivo. L-lysine also improves the functional recovery of ICH animals in neurobehavioral tests. Consistent with the role of PTEN in regulating inflammatory response, we find that PTEN inhibition promotes M2 microglial polarization and suppresses pro-inflammatory response in mouse ICH injury, which contribute to the neuroprotective effect of L-lysine. Moreover, our results reveal that microRNA-575 directly suppressed PTEN to promote M2 microglial polarization and mediate the neuroprotective effect of L-lysine in ICH injury. Together, our results suggest that L-lysine confers neuroprotection after ICH injury through enhancing M2 microglial polarization and reducing inflammatory response, which is mediated by microRNA-575 upregulation and subsequent PTEN downregulation.