针刺过程中穴位局部腺苷等化学物质关联及其与针刺效应的关系

Recently the role of local adenosine and other chemicals in the activation process in acupuncture analgesia attracted wide interests. However the sources and mechanisms of adenosine's function in the acupoint are not yet clear. Based on animal models and strict experimental design, this study attempts to answer the sources and targets of adenosine in the acupoint. In the first part to study the interaction between adenosine and other local structures in the acupoint, in acute adjuvant arthritis rats, the adenosine concentration in the acupoint during acupuncture, as well as the analgesia effects induced by administration of adenosine A1 agonist in the acupoint will be tested after acupoint pretreatment of collagenase, mast cell stabilizer and histamine H1 receptor antagonist respectively. In the second part to study the mechanism of increase of adenosine concentration in the acupoint during acupuncture and the involvement of mechanical sensitive channals, in inflammatory pain model of both normal and TRPV2 knock down mice, the adenosine concentration in the acupoint will be recorded during acupuncture after acupoint pretreatment of Cytochalasin B, TRPV2 antagonist respectively. Based on these studies on the sources, targets and mechanisms of local adenosine in acupuncture, we could be able to present a clearer understanding of local adenosine's function in the activation of the acupuncture analgesia effect, which would eventually benefit the clinic and refresh our understanding of acupuncture.

近年关于穴位腺苷等化学物质在针刺镇痛中的机制问题引起科学界广泛兴趣。但至今针刺腺苷物质来源和作用机制尚未阐明。本研究试图以模型和模式动物为基础，通过严密的实验设计，回答上述这个国际针灸界关注的热点问题。本研究在急性佐剂型关节炎大鼠上，用胶原酶、肥大细胞稳定剂、组胺H1受体拮抗剂等药物对穴位处的特定结构进行干预，检测针刺引起腺苷浓度升高和腺苷受体激动剂引起镇痛效应，阐明在针刺镇痛过程中穴位处腺苷与局部其他结构的相互作用机制。另外，在炎症痛小鼠模型基础上，使用TRPV2基因剔除小鼠以及细胞松弛素B、TRPV2拮抗剂穴位预处理等手段，检验机械敏感性蛋白与针刺中穴位腺苷浓度升高之间的关系。通过以上对于穴位处腺苷来源、作用对象和机械敏感性机制的研究，阐明针刺穴位腺苷物质在镇痛中的作用机理，并给出作用路径图，为解释针刺穴位机制提供科学依据。

近年关于穴位腺苷等化学物质在针刺镇痛中的机制问题引起了科学界广泛兴趣。为研究针刺过程中穴位处腺苷来源、作用对象和机械敏感性机制，本研究利用了急性佐剂型关节炎大鼠研究了肥大细胞稳定剂、组胺H1受体拮抗剂等药物对穴位处腺苷浓度升高过程以及腺苷A1受体激活引起镇痛效应的影响。项目针对TRPV2机械敏感性蛋白，利用炎症痛小鼠模型，研究了基因敲除小鼠以及通道拮抗剂对针刺过程中腺苷浓度变化的影响。我们发现：肥大细胞是引起针刺过程中穴位腺苷升高的关键，针刺效应信号物质组胺并未通过其H1受体影响腺苷浓度升高，腺苷和组胺信号存在并行的关系；穴位局部腺苷通过激活其A1受体引起镇痛效应，肥大细胞不是腺苷的穴位作用对象，腺苷信号是肥大细胞的下行信号；穴位处细胞受力学刺激激活释放腺苷的过程与细胞膜上通道有关，TRPV2通道拮抗剂可以抑制针刺引起的腺苷浓度变化。本研究指出了针刺刺激在穴位处如何转换为有效生物信号，确立了穴位组织胶原-TRPV蛋白-肥大细胞的信号启动通路，明确了穴位腺苷-组胺在穴位信号启动中的重要作用，给出了穴位局部腺苷参与针刺镇痛的路线图，为解释针刺疗法机制提供了新的科学证据。