a7nAchR/miR210信号通路在中枢胆碱能抗炎通路调控免疫性炎症的作用及机制研究

Immune abnormal mediated inflammation may deteriorate dopaminergic neurons damage of Parkinson's disease (PD). However, effective strategies are absent currently. It has been reported that an endogenous cholinergic anti-inflammatory pathway existed in brain, similar to that in the peripheral system, which was charactered by activation of a7 nicotinic acetylcholine receptor (a7nAchR). a7nAchR and miR210 are also associated with inflammation and T cell differentiation, respectively. In our previous studies, we found that activation of a7nAchR within the brain could upregulate the expression of miR210, suppress immune-inflammatory response and reduce neuron death.T cell differentiation is closely associated with neuroinflammation.Therefore, we speculated that miR210 might participate in the process that the central cholinergic anti-inflammatory pathway regulated the differentiation of T cells, and reduced the immune-inflammatory injury of PD. In this study, we adopted the 6-hydroxydopamine to make the PD models, also cultivated CD4+ T cells and induced its differentiation in vitro. We investigated the effectiveness of the cholinergic anti-inflammatory pathway on the regulation of immune-inflammation from the whole, tissue, cell and molecular levels, which would provide new direction and new target for PD treatment.

免疫功能异常介导的炎症反应可加重帕金森病（Parkinson's disease，PD）多巴胺能神经元损伤，目前仍缺乏有效调控措施。研究发现脑内存在类似外周的胆碱能抗炎通路，并且a7烟碱型乙酰胆碱能受体（a7 nicotinic acetylcholine receptor,a7nAchR）、miR210与炎症、T淋巴细胞分化相关；我们前期研究发现激活脑内细胞表面a7nAchR可增加miR210表达，同时抑制缺血后炎症反应，减少神经元凋亡。T淋巴细胞分化与神经炎症密切相关。因此，我们推测miR210参与中枢胆碱能抗炎通路调控T淋巴细胞分化，减少PD免疫性炎症损伤。本实验采用6-羟基多巴胺诱导PD模型及体外CD4+T淋巴细胞分化培养模型，从整体、组织、细胞水平改变a7nAchR、miR210表达研究中枢胆碱能抗炎通路调控免疫性炎症反应及分子机制，为PD治疗提供新方向和靶点。