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氨溴索上调葡萄糖脑苷脂酶表达,通过缺血性中风后的Wnt/β-连环蛋白通路促进神经干细胞分化为神经元。

Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke.

作者信息

Ge Hongfei, Zhang Chao, Yang Yang, Chen Weixiang, Zhong Jun, Fang Xuanyu, Jiang Xuheng, Tan Liang, Zou Yongjie, Hu Rong, Chen Yujie, Feng Hua

机构信息

Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

出版信息

Front Mol Neurosci. 2021 Jan 20;13:596039. doi: 10.3389/fnmol.2020.596039. eCollection 2020.

Abstract

Ischemic stroke has been becoming one of the leading causes resulting in mortality and adult long-term disability worldwide. Post-stroke pneumonia is a common complication in patients with ischemic stroke and always associated with 1-year mortality. Though ambroxol therapy often serves as a supplementary treatment for post-stroke pneumonia in ischemic stroke patients, its effect on functional recovery and potential mechanism after ischemic stroke remain elusive. In the present study, the results indicated that administration of 70 mg/kg and 100 mg/kg enhanced functional recovery by virtue of decreasing infarct volume. The potential mechanism, to some extent, was due to promoting NSCs differentiation into neurons and interfering NSCs differentiation into astrocytes through increasing GCase expression to activate Wnt/β-catenin signaling pathway in penumbra after ischemic stroke, which advanced basic knowledge of ambroxol in regulating NSCs differentiation and provided a feasible therapy for ischemic stroke treatment, even in other brain disorders in clinic.

摘要

缺血性中风已成为全球范围内导致死亡和成人长期残疾的主要原因之一。中风后肺炎是缺血性中风患者常见的并发症,且总是与1年死亡率相关。尽管氨溴索治疗常作为缺血性中风患者中风后肺炎的辅助治疗,但它对缺血性中风后功能恢复的影响及其潜在机制仍不清楚。在本研究中,结果表明,给予70mg/kg和100mg/kg剂量可通过减少梗死体积来促进功能恢复。其潜在机制在一定程度上是由于通过增加GCase表达以激活缺血性中风后半暗带中的Wnt/β-连环蛋白信号通路,从而促进神经干细胞分化为神经元并干扰神经干细胞分化为星形胶质细胞,这增进了对氨溴索调节神经干细胞分化的基础知识的了解,并为缺血性中风治疗乃至临床其他脑部疾病提供了一种可行的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ea/7855720/88ff5221214f/fnmol-13-596039-g0001.jpg

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