从改善肠道微生态-调节BNDF/TrkB信号通路探讨路氏八段锦治疗纤维肌痛症的疗效机制

Fibromyalgia (FM) is a rheumatic disease that is characterized by widespread pain throughout the body. The prevalence is ranked second of rheumatic diseases. There are limited pharmacotherapies for FM treatment and their efficacy is not satisfactory.Therefore, nonpharmacotherapy is generally recognized as a "first-line" therapy worldwidely.Lu Ba Duan Jin,modified from the traditional Ba Duan Jin,is based on unique understanding of health concept of a Chinese Medicine Master, Zhi-Zheng Lu.A previous clinical study has suggested that practicing Lu Ba Duan Jin could reduce body pain and fatigue and improve physical function and sleep quality, as well as lower the serum brain-derived neurotrophic factor (BDNF) level in patients with FM.The latest mechanism study of FM find that the imbalance of microbiome-gut-brain axis is likely to be one of the most important mechanisms of FM and Ba Duan Jin could regulate the intestinal microorganisms imbalance .Thus, it is speculated that one of the possible efficacy mechanisms of Lu Ba Duan Jin is to regulate the intestinal microorganisms imbalance and regulate the expression of central sensitive related BNDF/TrkB signal pathway.In this study,experiments in patients and FM animal model will be conducted to reveal the therapeutic mechanism of Lu Ba Duan Jin in the treatment of FM by forefront techniques such as metagenomics analysis ect.. Inheritance and excavation of famous traditional Chinese medicine master’s experience, expounding the scientific connotation of its theory will enhance the international influence of the nonpharmacotherapy therapy of Chinese Medicine in the treatment of FM.

纤维肌痛症(FM)是一种以全身广泛疼痛为主要表现的风湿病，患病率在风湿病中排名第二，治疗FM药物品种有限，疗效不尽如人意，非药物疗法是国际公认一线疗法。路氏八段锦是国医大师路志正老养生理念的升华，前期临床研究显示习练路氏八段锦可以改善FM病情、下调患者血清中脑源性神经营养因子(BDNF)水平。结合近年发现的肠道菌群-肠-脑轴失衡的中枢敏化性疼痛机制和八段锦改善肠道微生物平衡的文献报道，推测，路氏八段锦治疗FM疗效可能机制之一是通过改善肠道微生态、调节中枢敏化BNDF/TrkB通路的表达，发挥治疗FM的作用。本研究拟采用宏基因组测序与分析及细胞生物技术，开展人体、动物实验，从控肠道菌群-肠-脑轴平衡角度揭示路氏八段锦治疗FM的疗效机制，研究成果将有助于传承和挖掘名老中医经验、阐释其理论的科学内涵、提升中医非药物疗法治疗FM的国际影响力。

纤维肌痛症作为发病率居第三位的慢性骨骼肌肉疼痛性疾病，严重影响着患者的生活质量并伴随着巨大的经济负担，目前认为中枢敏化是其主要的发病机制。路氏八段锦是国医大师路志正老养生理念的升华，课题组前期系列的临床研究显示习练路氏八段锦可以改善纤维肌痛症患者的病情、提高患者的生活质量，但作用机制尚不清楚阻碍了其在临床中的推广。本研究结合近年发现的肠道菌群-肠-脑轴失衡的中枢敏化性疼痛机制和八段锦改善肠道微生物平衡的文献报道，联合多组学技术及细胞生物技术，从调控肠道菌群-肠-脑轴平衡角度揭示路氏八段锦治疗纤维肌痛症的疗效机制，研究结果表明：1.纤维肌痛症患者有独特的肠道微生物模式，路氏八段锦可能通过调节以韦荣氏球菌属为代表的肠道微生物发挥治疗纤维肌痛症的作用。2.纤维肌痛症患者血清Pro-BDNF和BDNF的表达下调，TrkB的表达上调。路氏八段锦干预纤维肌痛症的疗效机制可能与纠正Pro-BDNF和BDNF下调有关，而八段锦对睡眠质量的改善作用可能与降低TrkB的表达有关。3. 路氏八段锦干预有效的纤维肌痛症患者的血清可以在上调纤维肌痛症模型鼠原代星形胶质细胞中BDNF的表达水平的同时，抑制纤维肌痛症大鼠原代星形胶质细胞增殖的潜力，从而抑制纤维肌痛症大鼠大脑皮质星形胶质细胞过度活化。. 本研究从临床和细胞两个维度，从宏观到微观两个层次验证假说：“路氏八段锦通过肠道-脑轴，调节肠道微生物、调控中枢敏化性疼痛相关的BDNF/TrkB 信号通路，发挥治疗纤维肌痛症的作用。”研究成果将有助于传承和挖掘名老中医经验、阐释其理论的科学内涵、提升中医非药物疗法治疗纤维肌痛症的国际影响力。