穴位敏化的Ca2+通道机制

穴位是针灸治疗的最基本单位，在疾病状态下会被“激活”，使之处于敏化状态，针刺这些体表敏化的穴位会放大穴位本身的生物学效应。尽管穴位敏化是一种神经源性炎性反应，但内脏疾病如何敏化穴位的分子机制却并清楚。研究表明，背根节神经元上表达各种电压门控Ca2+通道亚型，其中N、R及T型Ca2+通道在神经源性炎性痛、伤害性神经元痛敏化中发挥重要作用，而且与疼痛信号传递密切相关。因此，在本研究中，我们拟以胃溃疡穴位敏化小鼠模型为载体，结合电生理、光学、化学遗传学、HPLC、基因组学、基因工程学、生化等技术对Ca2+通道在穴位敏化中的作用及Ca2+通道调节和Ca2+通道介导CGRP和P物质产生进行研究，这不但有助于从多维分子角度说明穴位敏化的机制和生物学基础，而且，对阐明穴位是什么，回答针灸关键科学问题具有重要科学价值，对临床科学选穴和智能诊疗装备研发也具有重要指导意义。

Acupoint, as an essential element in acupuncture, could be activated and sensitized in pathological conditions. Acupuncture at the sensitized acupoint can amplify its biological effects. The molecular mechanisms by which visceral disorders sensitize acupoints remain elusive whereas acupoint sensitization is neurogenic inflammation. Previous studies demonstrated that N-, R- and T-type calcium channels expressing in dorsal root ganglion (DRG) play an critical role in neurogenic inflammation，pain hypersensitization of nociceptive neurons and signal transmission. In present study, using electrophysiology, optics, chemogenetics, HPLC, genomics, genetic engineering, immunohistochemistry, etc., we will investigate the role of calcium channels in peripheral acupoint sensitization, the regulation of calcium channels and calcium channel-mediated release of CGRP and substance P in combined gastric ulcer and acupuncture sensitization mouse model. Our finding will not only be helpful for elucidating the molecular mechanism responsible for acupoint sensitization and biological basis, but also provide valuable evidence for explaining what acupoint is, redefining the acupoint, answering the key question in acupuncture area, and thus guide the prescription of acupoints in clinic.