大麻碱受体及PI3K-AKT通路与肥大细胞功能相关性及其机制探讨

Mast cell is an important effector cell of mediating allergic reaction. However, recent studies indicate that the activation of mast cell takes part in progress of many human inflammation-associated diseases, such as autoimmune disease, chronic inflammation and cancer. So investigating the molecule pathway of mast cell function and activation is important for understanding the mechanism of these human inflammation-associated diseases. Cannabinoid receptor and its downstream PI3K-AKT pathway also play important role in regulating human inflammation-associated diseases, and many studies indicate that cannabinoid receptor and PI3K-AKT pathway also regulate the function of mast cell, respectively, but the exactly mechanism is still unknown. To investigate the mechanism of cannabinoid receptor and its downstream PI3K-AKT pathway in regulating mast cell activation in vivo, we want to establish a mast cell specific transgenic zebrafish line. In use of a cannabinoid receptor 2 knockout zebrafish line and cannabinoid receptor agonists, we could investigate cannabinoid receptor and its downstream PI3K-AKT pathway in activation and relevant mechanism of mast cell by inducing inflammation of transgenic zebrafish embryos in vivo. Our study would contribute to understanding the mechanism of human inflammation-associated diseases and potential drug-candidate discovery by whole-organism chemical screen.

肥大细胞是介导过敏反应的主要效应细胞，但近年来大量研究表明肥大细胞的活化参与调节了许多人类免疫相关疾病的发病进程，如自身免疫病，慢性炎症和肿瘤等，因此研究肥大细胞的功能及相关通路对于我们了解这些疾病的机制具有重要意义。大麻碱受体及其下游PI3K-AKT通路同样对这些人类免疫相关疾病有着重要的调控作用，且有研究证实大麻碱受体和PI3K-AKT通路分别能够调节肥大细胞的功能，但具体机制依然值得进行深入研究。本课题通过建立肥大细胞以绿色荧光蛋白特异性标记的转基因斑马鱼系，利用大麻碱处理以及大麻碱受体突变的斑马鱼突变株，人为诱发斑马鱼胚胎的炎症反应，研究大麻碱受体及其下游PI3K-AKT通路对肥大细胞活体状态下在炎症反应中的功能相关性及其机制，对于我们深入了解炎症相关疾病的发病机制，进一步寻找潜在的治疗靶点和筛选小分子药物等，均具有重要意义。