肥大细胞(MC)是哮喘慢性炎症发生发展过程中关键的触发细胞和效应细胞，致敏的MC大量合成组胺等炎性介质，以脱颗粒形式释放导致哮喘发作，但其机制不甚明了。本课题组前期工作已证实：MC富表达神经钙传感蛋白NCS-1；哮喘致敏的MC中NCS-1表达显著增加，其活化态可激活Ca2+/CaMKⅡ信号通路，促进细胞内钙库释放，增加细胞内钙离子浓度([Ca2+]i)；同时囊泡质膜表达显著增强。由此我们推测NCS-1通过激活 Ca2+/CaMKⅡ信号通路正向调控MC钙触发的分泌囊泡脱颗粒，释放组胺等导致哮喘发作。在建立哮喘大鼠模型的基础上分离、纯化、浓缩和培养MC；采用siRNA干涉抑制或病毒载体细胞转染改变NCS-1表达，进一步检测MC中不同NCS-1水平对 Ca2+/CaMKⅡ信号通路及脱颗粒标志物组胺释放量的影响，从分子水平上深入地探讨哮喘的发病机制，为临床寻找哮喘干预的靶点提供理论依据。

Mast cells (MC) are pivotal trigger and effective cells in the development of chronic inflammation of asthma. Challanged MC can lead to asthma attack by synthesizing and then releasing histamine and other inflammatory mediators in the form of degranulation upon stimulation. However, the mechanism of this process is unclear. Preliminary work from our research group has already confirmed that MC shows a rich expression of neuronal calcium sensor protein(NCS-1); the NCS-1 expression is significantly increased in sensitized MC in asthma; NCS-1 binding with Ca2+ can activate Ca2+/CaMKII signal pathway and promote the release of intracellular calcium and an increase in the intracellular concentration of calcium ions; NCS-1 expression on the membrane of vesicles are significantly enhanced. Thus we speculate NCS-1 can trigger asthma attack by activating the Ca2+/CaMKII and increasing the level of histamine and other inflammatory mediators which released from MC secretory vesicles regulated positively by [Ca2+]i. On the basis of established model of asthmatic rats, the mast cells were isolated, purified, cultured and then used siRNA interference to suppress or transfected with virus vector to upregulate the expression of NCS-1. Furthermore, according to the different levels of NCS-1 expression in MC, the effect of NCS-1 on Ca2+/CaMK‖signal pathway were investigated to explore the pathogenesis of asthma identify by the release of histamine- - the marker of degranulation at the molecular level.It also provide the theortical evidence for finding new theraputic taget point in asthma.