电针刺激通过胆碱能神经-巨噬细胞轴介导Cajal间质细胞修复的机制研究

Cajal间质细胞（Interstitial cells of Cajal, ICC）的损伤或缺失是多种胃肠动力障碍性疾病的关键病理生理机制，申请人前期研究证实电针刺激可修复ICC网络，调节胃肠动力，但其具体机制不清。最近研究认为肌层巨噬细胞极化失衡与ICC损伤密切相关，而胆碱能神经信号是调节巨噬细胞活化的重要途径。因此，推测胆碱能神经信号调控巨噬细胞活化在电针刺激修复ICC过程中具有重要的作用。本项目将以胆碱能神经-巨噬细胞-ICC轴为主线，重点阐明电针刺激促进ICC修复的关键途径:1）电针刺激调节肌层巨噬细胞M1/M2极化水平修复ICC的分子机制；2）电针刺激通过β2烟酸样胆碱能受体和α7烟酸样胆碱能受体对肌层巨噬细胞活化及ICC损伤修复的调控作用。本研究将为电针刺激在胃肠动力障碍性疾病临床治疗中的应用提供理论依据。

The injured or missed ICC is the pivotal physiopathologic mechanism for a variety of gastrointestinal motility disorders. Our previous researches have confirmed that electroacupuncture at ST-36 could restore the networks of ICC and further regulate the gastrointestinal motility. However, the specific mechanism is not clear. The recent researches found that the injured ICC was closely related with the unbalanced polarized macrophages in muscularis and the cholinergic nerve signaling was the vital pathway to regulate macrophages activation. Therefore, we speculate that the cholinergic nerve signaling regulating the activation of muscularis macrophages may play an important role during the processes of electroacupuncture stimulation repairs ICC. The project will mainly clarify the key pathway of electroacupuncture restoring ICC with the axis of cholinergic nerve signaling-macrophages-ICC :1) the molecule mechanisms of electroacupuncture regulate the M1/M2 polarized level of muscularis macrophages on restoring ICC; 2) electroacupuncture regulates the muscularis macrophages activation and the ICC restoration by β2 nicotinic acetylcholine receptor and α7 nicotinic acetylcholine receptor. This research will supply theoretical foundation for the clinical application of electroacupuncture on treating gastrointestinal motility disorders.