Oxymatrine Extends Survival by Attenuating Neuroinflammation in a Mouse Model of Amyotrophic Lateral Sclerosis
Oxymatrine Extends Survival by Attenuating Neuroinflammation in a Mouse Model of Amyotrophic Lateral Sclerosis
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DOI：
10.1016/j.neuroscience.2021.04.019
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发表时间：
2021-05
期刊：
影响因子：
3.3
通讯作者：
Jian Zhang;Dongxia Li;Guofeng Yang;Xiangjian Zhang;Lin Chen;Yingzhen Zhang;Xiaoming Qi;Yi Li;Yansu Guo
中科院分区：
文献类型：
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作者：
Jian Zhang;Dongxia Li;Guofeng Yang;Xiangjian Zhang;Lin Chen;Yingzhen Zhang;Xiaoming Qi;Yi Li;Yansu Guo
肌萎缩侧索硬化症（ALS）是世界范围内与神经退行性疾病相关的主要死亡原因之一，并且该疾病的进展特征性地伴随着严重的神经炎症。氧化苦参碱（OMT）的神经保护作用是由于减少阿尔茨海默病和帕金森病小鼠模型中的神经炎症。本研究探讨OMT是否具有治疗潜力的转基因SOD 1-G93 A（TgSOD 1-G93 A）小鼠。每日OMT治疗从55日龄开始，直到疾病结束阶段。从70日龄开始，每3天评估一次体重和转棒运动性能。在治疗开始后40天和60天记录足迹以测量步幅。在115日龄时处死部分动物，收获腰髓进行免疫荧光和定量实时聚合酶链反应（qRT-PCR）以评价神经炎症反应。结果表明，用OMT治疗延迟了体重减轻，改善了运动表现，并延长了SOD 1-G93 A小鼠的存活时间。从机制上讲，OMT治疗增强了运动神经元的存活率，并减轻了小胶质细胞和星形胶质细胞的活化。OMT治疗组与对照组相比，促炎介质表达下调，抗炎因子表达上调（P< 0.05）。因此，OMT治疗具有神经保护作用，通过抑制神经炎症促进神经元存活并延长SOD 1-G93 A小鼠的寿命。
Amyotrophic lateral sclerosis (ALS) is one of the leading causes of death associated with neurodegenerative diseases worldwide, and the progression of the disease is characteristically accompanied by severe neuroinflammation. Neuroprotective effects of oxymatrine (OMT) were shown to be due to reduced neuroinflammation in the mouse models of Alzheimer’s disease and Parkinson’s disease. The present study investigated whether OMT has a therapeutic potential in transgenic SOD1-G93A (TgSOD1-G93A) mice. Daily OMT treatment started at the age of 55 days until the end stage of the disease. Body weight and rotarod motor performance were assessed every 3 days starting from 70 days of age. Footprints were recorded to measure the stride length 40 days and 60 days after the initiation of the treatment. Some animals were sacrificed at the age of 115 days, and the lumbar spinal cord was harvested for immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR) to evaluate the neuroinflammatory responses. The results indicated that treatment with OMT delayed body weight loss, improved motor performance, and prolonged the survival of SOD1-G93A mice. Mechanistically, OMT treatment enhanced motor neuronal survival and alleviated the activation of microglia and astrocytes compared with those in the vehicle-treated group. Furthermore, the expression of the proinflammatory mediators was downregulated, and the expression of the anti-inflammatory factors was upregulated in the OMT-treated group compared with those in the vehicle-treated group (P< 0.05). Thus, the treatment with OMT had neuroprotective effects, promoting neuronal survival and extending the lifetime of SOD1-G93A mice by suppressing neuroinflammation.