金属硫蛋白2及其结合蛋白介导的针刺抗哮喘舒张气管平滑肌效应机制研究

本项目建立在临床有效的针刺治疗方法和前期针刺抗哮喘效应物质基础研究有所发现基础之上。利用基因组学技术发现金属硫蛋白2(MT-2)是重要的针刺抗哮喘差异表达因子，且针刺能显著提高该蛋白在哮喘中表达。预初研究表明MT-2重组蛋白具有一定剂量范围内降低哮喘大鼠气道阻力和舒张气管平滑肌细胞作用，且该效应与MT-2已知生物学特性无关，提示MT-2在气管平滑肌细胞表面可能存在相应结合蛋白。本项目拟从哮喘动物模型、离体气管螺旋条模型、气管平滑肌细胞等层面研究MT-2蛋白对哮喘呼吸功能和气管平滑肌收缩舒张功能影响；利用基因敲除小鼠，研究MT-2在哮喘发病和针刺抗哮喘效应中的关键作用；寻找并确定MT-2在气管平滑肌细胞表面可能的结合蛋白，明确MT-2舒张气管平滑肌效应下游信号通路和潜在机制，从而科学地阐释针刺抗哮喘作用生物学内涵，为哮喘气管平滑肌收缩舒张功能提供新的调控靶点和机制。

This project is based on a clinically proven method for asthma and the research progress of the anti-asthmatic effect of acupuncture. Previous studies have shown that metallothionein 2 (MT-2) was one of the most important factors in asthma and acupuncture could significantly increase its expression. Preliminary experiments found that the MT-2 recombinant protein could reduce the airway resistance of asthmatic rat and relax the airway smooth muscle in a dose dependent manner. However, the relaxation effect was not related with the usual biological characteristics of MT-2, which suggested that the specific binding protein might exist on the surface of the airway smooth muscle cell. The study aims to test the biological functions of MT-2 in asthma from the aspects of animal model of asthma, isolated tracheal spiral model, and airway smooth muscle cell; use gene knockout mice to study the role of MT-2 in the pathogenesis of asthma and the regulation mechanism of acupuncture; after confirmation of the binding protein of MT-2, the downstream signaling pathways and the potential mechanism will be discussed. The study will scientifically explain the biological basis of the anti-asthmatic effect of acupuncture, and may provide new targets and regulation mechanism for airway smooth muscle contraction in asthma.