基于胆碱能抗炎通路研究针刺治疗COPD的作用机制

The morbidity and mortality of Chronic Obstructive Pulmonary Disease (COPD) is increasing year by year, which has become a heavy financial burden in the world. Acupuncture, improving the clinical symptoms and life quality of COPD patients, has attracted great concern of scholars in Japan and Germany. So, research on acupunctural mechanism is particularly urgent today. The main pathophysiological process in COPD is a chronic inflammation of the lungs and small airways and caused pulmonary function decline. Acupuncture has been used to treat inflammatory diseases, and the recent discovery of the cholinergic anti-inflammatory pathway (CAP) is widely involved in inflammation suppression. Therefore, basing on past works and preliminary experiments, the hypothesis is posed that, acupuncture has anti-inflammatory effect for COPD through the CAP, i.e, acupuncture can regulate the release of acetylcholine (Ach) in cholinergic nerve endings of lungs and small airways, which bind specific receptors 7nAChR on macrophage cell membrane and inhibit the release of inflammatory mediators through signal pathway of NF-κB、Jak2/STAT3, then slow down the inflammation and tissue damage and improve lung function. Experiment protocols is devised to treat COPD rats using electric needle on Feishu, and Zusanli points, to evaluate the acupuncture effect on the CAP from cell molecule,tissue and system level. This study will provide experimental evidence for the nerve-immune modulation mechanism of acupuncture treatment of COPD.

慢性阻塞性肺疾病（COPD）的发病率及死亡率正逐年上升，已成为全球沉重的经济负担，针刺能显著改善COPD患者的肺功能和提高生活质量，已引起日德学者的高度关注，目前对其作用机制的研究已显得尤为紧迫。COPD的病理特点是肺及小气道的慢性炎症及由此而致的肺通气功能下降；已知针刺具有抗炎效应，且最近发现胆碱能抗炎通路(CAP)广泛参与炎症抑制。故本课题在以往的工作及预实验的基础上提出假说：针刺能通过CAP对COPD发挥抗炎治疗作用，也即针刺通过调节胆碱能神经末梢释放ACh，与肺及小气道上的巨噬细胞特异受体7nAChR结合，通过胞内NF-κB、Jak2/STAT3信号途径，抑制炎性介质的释放，减缓炎症的发展和组织损伤，从而改善肺通气功能。实验拟用电针针刺COPD模型大鼠的肺俞、足三里穴，分别从分子细胞、组织及整体水平观察针刺对CAP的影响。本研究可为针刺治疗COPD的神经-免疫调节机制提供实验依据。

慢性阻塞性肺疾病（COPD）是以持续性的气流受限为特征的慢性肺部疾病，气道及肺实质的炎症性改变为其重要病理特点，临床文献及前期我们的动物实验研究均证实针刺可有效提高COPD的肺通气功能，减轻气流受限的症状。胆碱能抗炎通路（CAP）是沟通神经系统与免疫系统的调节通路，且研究已表明CAP可能参与了针刺抗炎的过程。那么，针刺是否可以通过该条通路，进而抑制COPD的炎症反应，改善肺功能而起到治疗作用？因而，我们利用香烟烟熏联合气管滴注脂多糖的方法复制COPD大鼠模型，观察针刺对COPD模型大鼠的抗炎效应，观察针刺对COPD大鼠迷走神经的放电、对肺组织内CAP相关环节关键物质（ACh、α7nAChR受体、受体后炎症信号通路NF-κB,JAK2-STAT3等）的影响，离体观察肺泡巨噬细胞经香烟烟雾提取物（CSE）诱导的炎性因子的表达及针刺血清的干预。通过在体研究，我们发现针刺COPD有确切的抗炎效应，针刺能激活迷走神经，下调CAP各环节物质的表达；离体实验证实了CAP参与了针刺血清对CSE诱导的炎性因子的调节，实验验证了我们提出的假说，完成预期的研究目标，研究结果表明电针大鼠双侧“足三里”和“肺俞”穴可改善COPD模型大鼠的肺功能，减轻炎症反应，其作用机制与激活迷走神经，抑制CAP受体后炎症信号通路有关。该项目研究可为临床推广应用针刺治疗COPD提供详实的实验证据，同时也为COPD的抗炎治疗提供潜在的药物治疗靶点。