Matrine ameliorates cognitive deficits via inhibition of microglia mediated neuroinflammation in an Alzheimer's disease mouse model
Matrine ameliorates cognitive deficits via inhibition of microglia mediated neuroinflammation in an Alzheimer's disease mouse model
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DOI：
10.1691/ph.2020.0395
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发表时间：
2020-07-01
期刊：
影响因子：
1.6
通讯作者：
Yao, Yao
中科院分区：
文献类型：
--
作者：
Li, Juan;Cheng, Xiao-Yu;Yao, Yao
β淀粉样蛋白（A β）诱导的小胶质细胞活化和伴随的神经炎症在阿尔茨海默病（AD）发病机制中起关键作用。苦参碱是从中草药苦参中提取的一种天然抗炎化合物。（库申）。本研究旨在探讨苦参碱对寡聚体A β（oA β）诱导的AD小鼠模型记忆障碍和神经炎症的影响。小胶质细胞活化和NADPH氧化酶是否参与了这些作用还有待进一步研究。脑室内注射oA β（2.5 μ g/pl，4 μ l）后，每天一次灌胃给予不同剂量的苦参碱（10、20或40 mg/kg）。注射oA β后15天，进行行为学实验，包括新物体识别（NOR）实验和Morris水迷宫（MWM）实验。注射oA β后21天，评估小鼠海马组织中活性氧、肿瘤坏死因子-α、IL-1 β和IL-6的浓度以及NADPH氧化酶亚基gp 91 phox和p47 phox的表达，并通过lba-1免疫组织化学染色评估小胶质细胞的活化。NOR实验和MWM实验结果显示oA 6注射可明显损害AD小鼠的学习记忆功能，苦参碱可明显改善其损害。注射oA 6后ROS、TNF-α、IL-1 β和IL-6水平升高，而苦参碱可显著降低这些炎症因子的浓度。苦参碱还显著降低oA β诱导的NADPH氧化酶亚基gp 91 phox和p47 phox的蛋白表达。LBA-1免疫组化结果显示苦参碱处理的小鼠脑中活化的小胶质细胞较少。提示苦参碱能改善oA β所致的学习记忆障碍和神经炎症反应。这些作用被认为是通过抑制海马组织中的小胶质细胞活化和NADPH氧化酶表达来介导的。结果提示苦参碱可能是一种有价值的抗AD的天然化合物。
Amyloid beta (A beta) induced microglial activation and attendant neuroinflammation play pivotal roles in Alzheimer's disease (AD) pathogenesis. Matrine is a natural anti-inflammation compound from the Chinese herbal medicine Sophora flavescens Ait. (Kushen). This study aimed to investigate the effects of matrine on memory deficit and neuroinflammation in an oligomeric A beta (oA beta)-induced AD mice model. Whether microglial activation and NADPH oxidase were involved in these effects were further studied. Different doses of matrine (10, 20, or 40 mg/kg) were intragastrically administered once a day after intracerebroventricular oA beta injection (2.5 mu g/pl, 4 mu l). 15 days after the oA beta injection, behavioral experiments including novel object recognition (NOR) test and Morris water maze (MWM) test were performed. 21 days after the oA beta injection, concentration of ROS, TNF-alpha, IL-1 beta and IL-6 as well as expression of NADPH oxidase subunits gp91phox and p47phox in mice hippocampal tissues were assessed, and microglial activation were evaluated by lba-1 immunohistochemical staining. Results of NOR test and MWM test revealed that oA6 injection could remarkably impair learning and memory function in AD mice, and matrine administration could significantly ameliorate the impairment. ROS, TNF-alpha, IL-1 beta and IL-6 levels increased after oA6 injection, while matrine could significantly reduce the concentrations of these inflammatory factors. oA beta induced protein expression of NADPH oxidase subunits gp91phox and p47phox were also significantly reduced by matrine. lba-1 immunohistochemistry results showed less activated microglia in matrine-treated mice brain. These results indicate that matrine could ameliorate learning and memory impairment and neuroinflammation induced by oA beta injection. These effects were found to be mediated through inhibition of microglial activation and NADPH oxidase expression in hippocampal tissue. The results suggest that matrine may be a valuable natural compound with therapeutic potential against AD.