降钙素基因相关肽（Calcitonin gene-related peptide, CGRP）对穴位敏化的调节及机制研究

Acupoint plays an essential role in acupuncture. The sensitized acupoints are a series of cutaneous phenotypes induced by pathological conditions. Acupuncture at the sensitized acupoint can amplify its biological effect. Previous studies have demonstrated that acupoint sensitization is a cutaneous phenomenon of neurogenic inflammation caused by visceral diseases. However, the molecular mechanism responsible for acupoint sensitization still remains elusive. Calcitonin gene-related peptide (CGRP) is expressed in Aδ和C fibers in peripheral nervous system, and play an important role in neurogenic inflammation and nociceptive sensitization. It can intensify neurogenic inflammation and facilitate the sensitization of peripheral nociceptive neurons. In present study, using the combined techniques such as genetic engineering, chemogenetics, immunohistochemistry, optics and electrophysiology, etc., we will investigate the role of CGRP in acupoint sensitization and the underlying mechanisms in C57BL/6, CGRPα-GFP and CGRPα-DTR+/- mice, etc. Our findings will not only provide an valuable evidence for elucidating the molecular mechanisms by which acupoint sensitization is induced, but also elucidate what the acupoint is, whether the acupoint exist, and thus be helpful to the prescription of acupoints in treatment of visceral diseases.

穴位是针灸治疗的最基本要素之一。穴位敏化是机体于病理状态下被激活的体表反应。在这些被敏化的反应点针刺可能会放大穴位本身的生物学效应。尽管已有研究证明穴位敏化现象是内脏病变通过神经源性炎性反应在体表的体现，但是，敏化穴位形成的分子机制却并不清楚。已有研究表明，在外周神经Aδ和C纤维中高表达的降钙素基因相关肽（CGRP），在神经源性炎症及伤害性痛敏化过程中发挥重要作用，在多个水平可强化神经源性炎症和外周痛觉神经元的敏化。在本研究中，我们拟以C57BL/6、CGRPα-GFP和CGRPα-DTR+/-等小鼠制作胃溃疡模型/敏化模型，结合基因工程学、化学遗传学、免疫组织化学、光学、电生理及生化等技术对CGRP在穴位敏化中的作用进行研究并阐明其作用机制，这不但对阐明穴位敏化的分子机制具有重要价值，而且，对阐明“穴位是什么”，“穴位是否存在”及针刺治疗内脏疾病的选穴也具有重要指导意义。

穴位是针灸治疗的最基本要素之一。穴位敏化是机体于病理状态下被激活的体表反应。在这些被敏化的反应点针刺可能会放大穴位本身的生物学效应。尽管已有研究证明穴位敏化现象是内脏病变通过神经源性炎性反应在体表的体现，但是，敏化穴位形成的分子机制却并不清楚。已有研究表明，在外周神经Aδ和C纤维中高表达的降钙素基因相关肽（CGRP），在神经源性炎症及伤害性痛敏化过程中发挥重要作用，在多个水平可强化神经源性炎症和外周痛觉神经元的敏化。在本研究中，我们以C57BL/6、CGRPα-GFP和CGRPα-DTR+/-等小鼠制作胃溃疡模型/敏化模型，结合基因工程学、化学遗传学、免疫组织化学、光学、电生理及生化等技术对CGRP在穴位敏化中的作用进行研究并阐明其作用机制。研究结果表明：胃溃疡模型小鼠体表敏化区及DRG中的CGRP和TRPV1表达增加；脊髓T9-T11节段内的DRG中、小型神经元通过不同的放电活动参与小鼠胃溃疡介导的穴位敏化过程；DRG神经元的内在兴奋性、Na+通道动力学改变与CGRP表达的改变密切相关。这不仅为针灸治疗内脏疾病提供科学证据，对阐明“穴位是什么”，“穴位是否存在”也具有重要指导意义。