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麝香酮通过激活PI3K/Akt信号通路诱导脑缺血中神经干细胞的增殖和分化。

Musk Ketone Induces Neural Stem Cell Proliferation and Differentiation in Cerebral Ischemia via Activation of the PI3K/Akt Signaling Pathway.

作者信息

Zhou Zheyi, Dun Linglu, Wei Bingxin, Gan Yanyan, Liao Zhongling, Lin Xiumiao, Lu Junlei, Liu Guocheng, Xu Hong, Lu Changjun, An Hongwei

机构信息

Department of Neurology, Liuzhou Traditional Chinese Medical Hospital, the Third Affiliated Hospital of Guangxi University of Chinese Medicine, Liuzhou 545001, PR China.

Department of Neurology, Liuzhou Traditional Chinese Medical Hospital, the Third Affiliated Hospital of Guangxi University of Chinese Medicine, Liuzhou 545001, PR China.

出版信息

Neuroscience. 2020 May 21;435:1-9. doi: 10.1016/j.neuroscience.2020.02.031. Epub 2020 Feb 27.

DOI:10.1016/j.neuroscience.2020.02.031
PMID:32112919
Abstract

Traditional Chinese medicine has been reported to influence the proliferation and differentiation of neural stem cells (NSCs) that may be protective against nervous system diseases. Recent evidence indicates the importance of musk ketone in nerve recovery and preventing secondary damage after cerebral ischemic injury. A middle cerebral artery occlusion (MCAO) rat model was established by a transient filament model, and rats were treated with musk ketone (0.9 or 1.8 μM). Next, an in vitro oxygen-glucose deprivation (OGD) cell model was established to study the effect of musk ketone on the proliferation and differentiation of NSCs. To determine the potential mechanisms of musk ketone involved in activities of NSCs, the effect of musk ketone on the PI3K/Akt signaling pathway activation was assessed. Furthermore, NSCs were treated with musk ketone in the presence of PI3K/Akt inhibitor Akti-1/2 to examine their roles on NSC proliferation and differentiation. Musk ketone reduced cerebral ischemic injury in a dose-dependent manner in rats. In addition, NSCs treated with musk ketone showed enhanced proliferation and differentiation along with increased PI3K/Akt signaling pathway activation. The effects of muck ketone were reversed by Akti-1/2. Altogether, musk ketone promoted NSC proliferation and differentiation and protected against cerebral ischemia by activating the PI3K/Akt signaling pathway, highlighting the potential of musk ketone as a physiologically validated approach for the treatment of cerebral ischemia.

摘要

据报道,传统中药可影响神经干细胞(NSCs)的增殖和分化,这可能对神经系统疾病具有保护作用。最近的证据表明,麝香酮在神经恢复和预防脑缺血损伤后的继发性损伤方面具有重要作用。采用短暂性线栓法建立大脑中动脉闭塞(MCAO)大鼠模型,并用麝香酮(0.9或1.8 μM)对大鼠进行治疗。接下来,建立体外氧糖剥夺(OGD)细胞模型,以研究麝香酮对NSCs增殖和分化的影响。为了确定麝香酮参与NSCs活性的潜在机制,评估了麝香酮对PI3K/Akt信号通路激活的影响。此外,在PI3K/Akt抑制剂Akti-​​1/2存在的情况下,用麝香酮处理NSCs,以检查它们对NSC增殖和分化的作用。麝香酮以剂量依赖性方式减轻大鼠脑缺血损伤。此外,用麝香酮处理的NSCs显示出增殖和分化增强,同时PI3K/Akt信号通路激活增加。Akti-1/2可逆转麝香酮的作用。总之,麝香酮通过激活PI3K/Akt信号通路促进NSCs增殖和分化,并保护免受脑缺血的影响,突出了麝香酮作为一种经生理学验证的治疗脑缺血方法的潜力。

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