新近研制的大麻类物质（cannabinoids, CBs）对消化系统炎症性疾病表现出抗炎潜能，但其作用特点及机制有待明确。本课题组前期工作发现，丝裂原激活的蛋白激酶（MAPK）p38/MK2信号通路参与溃疡性结肠炎发病过程，CB受体激动剂WIN55,212-2的抗炎作用与抑制p38激活有关。本项目用C57BL小鼠野生型和CB1受体、CB2受体基因敲除型、p38MAPK /MK2基因干扰或敲除型，复制消化系统不同炎症疾病模型（溃疡性结肠炎、急性胰腺炎等）；通过分析比较CBs干预前后炎症相关指标的变化，如组织病理学改变、促炎细胞因子和化学趋化因子水平、远隔器官的损伤，以及这些变化在不同炎症模型中的异同，深入揭示CBs对消化系统炎症疾病的作用和特点、可能涉及的CB受体、与p38MAPK/MK2的关系等。为充实和完善相关疾病的发病机制及CBs的作用机制，为CBs的临床应用提供理论基础和实验依据。

The newly developed cannabis substances (cannabinoids, CBs) demonstrate anti-inflammatory potential on inflammatory digestive diseases,yet their effective characteristics and mechanism need to be clarified.Our previous studies have found that the mitogen-activated protein kinase (MAPK) p38/MK2 passway was involved in the pathogenisis of dextran sulfate sodium (DSS)-induced mouse ulcerative colitis, and the anti-inflammatory role of WIN55,212-2, an agonist of CB1/CB2 receptor was related to inhibition of p38 MAPK. In this project we intend to duplicate several common animal models of inflammatory digestive diseases, including DSS-induced ulcerative colitis, cerulein-induced acute pancreatitis and endotoxin(LPS)-induced gastrointestinal dysfunction in wild-type, CB receptor type 1 and type 2 knockout, and p38MAPK /MK2 gene interfered or knockout C57BL mice. The selected CBs for respective CB receptors will be applied for intervention and observation. By analyzing the dynamics of relevant inflammation indicators, such as histopathological changes,the levels of pro-inflammatory cytokines and chemokines, distant organ injuries, and the similarities and differences of the results in each inflammation model, we shall be able to reveal the characteristics and mechanism of the action of CBs on the inflammatory digestive diseases, and to ascertain the CB receptors involved, and the possible relationship between the CB system and p38MAPK/MK2 signal pathway in the action. This research will enrich our knowledge of the pathogenesis of relevant diseases and help understand the mechanism of the action of CBs, thus provide experimental evidences and theoretical guidelines for clinical application of CBs.