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| 通天草提取物对Aβ损伤SAMP8小鼠原代海马神经元细胞的保护作用及代谢组学研究 |
| Study of Waternut herb Extract On Aβ SAMP8 Damage of Mouse Hippocampal neurons and The Protective Effect of Metabolomic study |
| 投稿时间：2017-01-17 修订日期：2017-01-23 |
| DOI： |
| 中文关键词: 通天草 SAMP8小鼠 免疫组织化学染色方法 代谢足迹 潜在靶点 |
| 英文关键词: waternut herb SAMP8 mice immunohistochemistry metabolic footprinting potential target |
| 基金项目: |
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| 中文摘要: |
| 目的 采用代谢足迹技术对通天草提取物对Aβ损伤SAMP8小鼠原代海马神经元细胞的保护作用进行代谢机制研究。方法 采用免疫组织化学染色方法测定Aβ损伤SAMP8小鼠原代海马神经元细胞的细胞增殖情况,在此基础上首次采用代谢足迹技术评价通天草提取物的疗效。聚焦关键代谢通路及相关代谢靶标,阐明其Aβ损伤SAMP8小鼠原代海马神经元细胞的发病机制和通天草提取物的作用机制。结果 免疫组化染色发现海马区DG、CA1、CA3区的Ki67阳性细胞增殖减少,海马区发生损伤。经代谢足迹技术研究发现,与同窝野生小鼠相比,Aβ损伤SAMP8小鼠的原代海马神经元细胞代谢异常主要集中在与神经细胞相关的叶酸代谢和牛磺酸代谢上,经高通量质谱解析及文献数据库检索确定了3个差异代谢物,分别是L-磺基丙氨酸(L-Cysteic acid)、二氢叶酸(Dihydrofolate)、分支酸(Chorismate),这些小分子代谢产物经通天草提取物干预后有明显的回调趋势。结论 通天草提取物对Aβ损伤SAMP8小鼠的原代海马神经元细胞具有一定程度的治疗作用,本次发现的3个生物标记物可能是Aβ损伤SAMP8小鼠的原代海马神经元细胞发病机制的潜在靶点,给予通天草提取物后这些标记物呈不同程度的回调趋势,提示通天草提取物可能通过调节相关代谢酶及代谢通路达到保护作用的目的,为通天草提取物治疗阿尔兹海默病提供实验依据。 |
| 英文摘要: |
| Objective To study the metabolic mechanism of protective effect of waternut herb extract on primary A beta SAMP8 damage of mouse hippocampal neurons by metabolic footprinting. Methods by using immunohistochemical staining method to detect cell proliferation of primary A beta SAMP8 damage of mouse hippocampal neurons, the effect for the first time on the basis of metabolic footprinting evaluation waternut herb extract. Focus on key metabolic pathways and related metabolic targets, mechanism of primary A beta SAMP8 damage of mouse hippocampal neurons and pathogenesis of waternut herb extract. Results immunohistochemical staining showed that Ki67 positive cells in DG, CA1 and CA3 decreased in hippocampus, and the hippocampus was damaged. The study found that metabolic footprinting, compared with littermate wild-type mice, neuronal cell metabolism A beta SAMP8 damage of mouse anomalies mainly concentrated in the metabolism of folic acid and taurine metabolism associated with nerve cells, by high-throughput mass spectrometric analysis and literature database retrieval to determine the 3 differential metabolites, respectively is L- disodoum alanine (L-Cysteic acid), dihydrofolate (Dihydrofolate), acid (Chorismate), the branch of small molecule metabolites through extract intervention after Amakusa callback trend obviously. Conclusion the therapeutic effect of waternut herb extract on A beta SAMP8 damage of mouse primary hippocampal neurons to a certain extent, 3 biomarkers of this discovery may be a potential target of A beta SAMP8 damage of mouse primary hippocampal neurons in the pathogenesis of waternut herb extract, given after these markers were callback trend in different degree, suggesting that waternut herb extract could regulate metabolism related enzymes and metabolic pathways to protect the purpose, to provide the experimental basis for the treatment of Alzheimer"s disease waternut herb extract. |
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