基于α7nAChR研究青藤碱调节神经免疫干预AD的作用机制

青藤碱（SIN）是中药青风藤的有效成分，项目前期研究明确了烟碱型乙酰胆碱受体α7（α7nAChR，简称α7）是SIN抗炎的关键靶点，我们最新研究发现SIN对阿尔兹海默病（AD）模型小鼠有神经保护作用。衰老伴随的神经和免疫系统功能失调是AD的基本特征。α7是机体神经免疫网络中胆碱能抗炎通路的关键受体，参与细胞增殖活化和免疫调节，参与神经细胞功能，也参与β 淀粉样多肽（Aβ）诱导的神经毒性。据此本研究提出SIN作用于α7调节神经免疫、作用于小胶质细胞和神经细胞α7调节细胞功能、干预AD进展的假设。通过分析AD模型动物外周炎症、神经炎症和脑组织病理变化与α7表达变化，以及小胶质细胞活化和神经细胞损伤中α7的作用，分析SIN作用于α7调节神经免疫对AD的干预机制。本研究为探讨SIN抗AD的临床应用价值、为丰富青风藤祛风通络的现代药理学内涵提供理论依据，也为中药抗AD研究提供新的思路

Sinomenine (SIN) is a major effective component of the Chinese materia medica Sinomenium acutum. Our team has elucidated that nicotinic acetylcholine receptor alpha 7 (α7nAChR) is the anti-inflammatory key target of SIN. Recently, we found SIN showed significant neuroprotective effect on Alzheimer’s disease model mice. The disorder of nervous and immune systems with age is the major characteristic of AD. α7nAChR, the key receptor of cholinergic anti-inflammatory pathway, is involved in cell activation and proliferation, and immunoregulation, and plays an important role in neuron function, but also neurotoxicity induced by β-amyloid peptide (Aβ ). So we forward hypothesis that SIN prevents AD development by regulating neuroimmune via α7nAChR. The anti-AD mechanism of SIN targeting α7nAChR will be revealed by analysis of the role of α7nAChR in the effect of SIN on periphery immunity, neuroinflammation, and pathological changes in brain, and on the microglia activation and neuron injury. From the angle of neuro-immune to study the mechanism of SIN act on α7nAChR to prevent AD development will provide theoretical basis for new clinical value of SIN, and be helpful to explain Qu-Feng-Tong-Luo function of Sinomenium acutum. The study will also provide a new strategy to study treatment of AD.