基于治未病理念针刺干预帕金森病前驱期非运动症状的作用机制研究

Parkinson's disease (PD) is a degenerative disease of the central nervous system mainly manifested with extrapyramidal dysfunction.Recent studies have proved that key pathogenic factors such as α-synuclein deposition and the release of inflammatory factors would spread gradually from gastrointestine to the central nervous system, inducing neuronal loss and ultimately leading to PD lesions. The deposition of α-synuclein is involved in the most common one of prodromalphase non-motor symptoms-constipation, it is also the factor to initiate various pathological changes to further accelerate the progress of PD. Studies have shown that acupuncture can effectively treat constipation. Previous studies also demonstrated that acupuncture exhibited effect on constipation. Our premilary data also proved that acupuncture could significantly delay the progress of PD via an improvement of constipation.Therefore, based on the the principle of preventive treatment, the present study will set PD animal models as the research subjects, and be carried out along the main line of α-synucleindeposition-inflammatory reaction-Microglia activation using combined techniques including praxiology, electrophysiology, and molecular biology. We will thus elucidate that acupuncture is able to delay the progress of PD through alleviation of constipation and the underlying mechanisms. Our results will provide convincing evidence for the scientific nature of non-motor symptoms of PD treatment and enrich the connotation of TCM preventive treatment-prodromalphase treatment to prevent deterioration.

帕金森病（PD）是一种以椎体外系功能障碍为主要表现的中枢神经系统退行性疾病。新近研究证实，α-突触核蛋白沉积、炎症因子释放等PD发病关键因素，由胃肠道逐渐播散至中枢神经系统，诱发神经元丢失，最终导致PD加重。便秘作为PD前驱期非运动症状之一，与肠神经元α-突触核蛋白的沉积密切相关，而α-突触核蛋白是加速PD发病进程的始动因素。研究表明，针刺可有效治疗便秘。我们前期工作证实，针刺疗法能有效干预PD模型前驱期非运动症状便秘，显著延缓PD发病进程。因此，本着“治未病”理念，本课题将以PD动物模型为研究对象，以“α-突触核蛋白-炎症反应-小胶质细胞活化”为主线，拟通过行为学、电生理学、分子生物学等实验手段，系统阐明针刺疗法通过干预PD前驱期症状便秘以延缓PD发病进程的效应与机制，以期为PD前驱期非运动症状治疗的科学性提供有力的实验证据，丰富中医学“既病防变”治未病的内涵。

帕金森病（PD）是一种以椎体外系功能障碍为主要表现的中枢神经系统退行性疾病。新近研究证实，α-突触核蛋白沉积、炎症因子释放等PD发病关键因素，由胃肠道逐渐播散至中枢神经系统，诱发神经元丢失，最终导致PD加重。便秘作为PD前驱期非运动症状之一，与肠神经元α-突触核蛋白的沉积密切相关，而α-突触核蛋白是加速PD发病进程的始动因素。研究表明，针刺可有效治疗便秘。因此，在本研究中，我们尝试在近来研究的基础上与国家重点基础研究发展计划（973 计划） 项目研究成果（针刺不同穴位对功能性肠病的双向调节作用及机制， NO.2011CB505204） 结合，基于中医“治未病”理念中的“既病防变”，以“α-突触核蛋白-炎症反应-小胶质细胞活化”为研究主线，基于“PD的病理改变始发于肠道，通过迷走神经逆行传播到中枢”的病理机制尝试从改善肠道功能障碍入手，运用行为学、分子生物学、神经示踪等实验手段，系统阐明针刺疗法早期干预非运动症状减缓帕金森病发展的分子生物学机制。研究结果表明针刺疗法对 PD 前驱期动物模型肠道功能障碍改善明显，并有延缓PD发病进程的趋势。研究结果不仅为临床治疗PD的研究提供新的思路和实验证据，而且对针灸与“治未病”理念的结合推广至其他慢性难治性疾病具有较大临床指导意义和推广应用前景。