10种香豆素衍生物神经保护作用筛选及机制初探

发布时间：2018-03-02 07:31

本文关键词： 香豆素衍生物神经保护炎症因子自由基　出处：《药学学报》2015年06期 　论文类型：期刊论文

【摘要】：检测10种新型香豆素衍生物的神经保护作用,并对其可能的机制进行初步探索。采用MTT法筛选10个香豆素衍生物对神经毒性剂(Aβ25-35及鱼藤酮)或氧糖剥夺(OGD)所致神经细胞损伤的保护作用,获得活性较好的化合物;采用显微形态学观察各种神经毒性剂模型下该化合物的作用情况;通过脂多糖(LPS)致小胶质细胞炎症病变,并采用ELISA法检测化合物对炎症因子的抑制作用;最后,检测此化合物对自由基的直接清除能力。化合物3不但对3种神经元毒性模型所致细胞存活率降低均有显著的改善作用,而且能显著抑制神经胶质细胞炎症模型中炎症因子(TNF-α,IL-1β)的释放。另外,化合物3具有很好的自由基清除能力,对超氧阴离子的清除能力相当于维生素C。化合物3显著的超氧阴离子的清除作用可能是其重要的神经保护机制。化合物3作为一种潜在的神经保护剂,值得进一步研究。
[Abstract]:The neuroprotective effects of 10 new coumarin derivatives were detected. The protective effects of 10 coumarin derivatives on nerve cell injury induced by neurotoxic agents A 尾 25-35 and rotenone were screened by MTT method. The micromorphology was used to observe the action of the compound in the model of neurotoxic agents, the inflammation of microglia was induced by lipopolysaccharide (LPS), and the inhibitory effect of the compound on inflammatory factors was detected by ELISA method. The direct scavenging ability of the compound to free radicals was tested. Compound 3 not only significantly improved the cell survival rate induced by three neuronal toxicity models, Moreover, the release of inflammatory factor TNF- 伪 and IL-1 尾 in glial inflammation model was significantly inhibited. In addition, compound 3 had good free radical scavenging ability. The scavenging ability of superoxide anion is equivalent to that of vitamin C. compound 3, which may be an important neuroprotective mechanism. Compound 3, as a potential neuroprotective agent, deserves further study.
【作者单位】：中国医学科学院神经科学中心中国医学科学院北京协和医学院药物研究所;
【基金】：国家自然科学基金资助项目(81274122,81173578,U1402221) 国家高技术研究发展计划资助项目(2012AA020303) 国家“重大新药创制”科技重大专项资助项目(2012ZX09103101-006,2012ZX09301002-001-002) 新药作用机制研究与药效评价北京市重点实验室资助项目(BZ0150)
【分类号】：R96

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