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.

中文翻译：

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小鼠脑出血损伤后，l-赖氨酸通过抑制经由microRNA-575 / PTEN信号传导的炎症反应而赋予神经保护作用。

1-赖氨酸是一种碱性氨基酸，已被证明具有神经保护作用。但是，尚需阐明其基本机制。在这项研究中，我们调查了l-赖氨酸如何在体外被血红素感染的小鼠皮质神经元和体内脑出血（ICH）的小鼠模型中发挥其神经保护作用。我们证明L-赖氨酸治疗促进M2小胶质细胞极化和减少体内和体外的炎症反应，表明L-赖氨酸可能在ICH损伤中起神经保护作用。确实，我们表明，L-赖氨酸治疗可减少体外血红素侵袭后皮质神经元的死亡，并减少体内ICH后变性神经元的数量。l-赖氨酸还可以改善神经行为试验中ICH动物的功能恢复。与PTEN在调节炎症反应中的作用一致，我们发现PTEN抑制作用可促进M2小胶质细胞极化并抑制小鼠ICH损伤中的促炎反应，这有助于L-赖氨酸的神经保护作用。此外，我们的结果表明，microRNA-575直接抑制PTEN以促进M2小胶质细胞极化并介导l-赖氨酸在ICH损伤中的神经保护作用。在一起，我们的结果表明，l-赖氨酸通过增强M2小胶质细胞极化和减少炎症反应而赋予了ICH损伤神经保护作用，这是由microRNA-575上调和随后的PTEN下调所介导的。有助于l-赖氨酸的神经保护作用。此外，我们的结果表明，microRNA-575直接抑制PTEN以促进M2小胶质细胞极化并介导l-赖氨酸在ICH损伤中的神经保护作用。在一起，我们的结果表明，l-赖氨酸通过增强M2小胶质细胞极化和减少炎症反应而赋予了ICH损伤神经保护作用，这是由microRNA-575上调和随后的PTEN下调所介导的。有助于l-赖氨酸的神经保护作用。此外，我们的结果表明，microRNA-575直接抑制PTEN以促进M2小胶质细胞极化并介导l-赖氨酸在ICH损伤中的神经保护作用。在一起，我们的结果表明，l-赖氨酸通过增强M2小胶质细胞极化和减少炎症反应而赋予了ICH损伤神经保护作用，这是由microRNA-575上调和随后的PTEN下调所介导的。