海风藤抑制Aβ诱导小胶质细胞活化的有效成分及机制研究

Activation of microglia plays an important role in the occurrence and progression of Alzheimer's disease (AD). Substantial bioactive substances produced by β amyloid protein-activated microglia can lead to neuron damage and promote progression of AD. So we can get a hopothesis that one target for drug intervention of AD is to inhibit abnormal microglia activation and reduce the release of neurotoxins. Our previous results showed that Kadsura Pepper could inhibit microglia activation and inflammatory reaction by pathomorphological, Western Blot, RT-PCR and other methods. However, the active ingredients and the mechanisms are still unknown. To lay a theoretical basis for further clinical application of Kadsura Pepper, we will extract and purify this drug using TLC, MS, NMR, RT-PCR, Western Blot and other methods, and then explore the active ingredient and preliminarily clarify the mechanism of inhibition of microglia activation by it.

小胶质细胞活化在阿尔茨海默病（Alzheimer's disease, AD ）发生发展中起重要作用。由β-淀粉样蛋白（β-amyloid, Aβ）沉积激活的小胶质细胞可产生大量生物活性物质，导致神经元损伤，加速AD发展。因此，抑制小胶质细胞异常活化及神经毒性物质释放将成为AD药物干预的靶点。我们既往运用病理形态学、Western Blot、RT-PCR等技术，初步证实了海风藤能抑制Aβ诱导的小胶质细胞激活和炎症反应。但其有效成分和可能机制目前尚不清楚。本课题拟采用活性追踪方法及薄层色谱（TLC）、质谱（MS）、核磁共振谱（NMR）等波谱技术对海风藤进行分离、提纯，并运用RT-PCR及Western Blot等方法初步确定海风藤抑制小胶质细胞异常活化的有效成分及其可能的作用机制，为进一步开发海风藤的临床应用奠定理论基础。

阿尔茨海默病（AD）是一种以进行性认知功能障碍、精神行为异常及生活能力减退为特征的慢性进行性神经系统退行性疾病，但AD的发病机制尚未完全阐明，目前也缺乏肯定、有效的治疗措施。研究表明β-淀粉样蛋白（Aβ）沉积导致小胶质细胞活化引起脑内慢性炎症反应可能在AD的发生发展中起着关键作用。我们既往初步证实了海风藤能抑制Aβ诱导的小胶质细胞激活和炎症反应，但其有效成分和可能机制目前尚不清楚。本课题拟将采用醇提取法分离萃取海风藤，得到石油醚、乙酸乙酯、正丁醇及醇残留相等4个不同的活性部位，将其作用于Aβ1-42寡聚体诱导激活的小胶质细胞。采用RT-PCR及Western Blot的方法检测了IL-1β和TNF-α等炎性因子的表达，初步明确抑制小胶质细胞异常活化的有效成分，为进一步开发利用海风藤奠定理论基础。