Analysis of anima models of inflammatory bowel disease and therapeutics application for inflammatory bowel disease

腺苷A（2A）受体的激活可减少各种促炎细胞因子的产生并抑制中性粒细胞的激活。众所周知，水浸约束和阿司匹林会引起胃粘膜病变。胃粘膜病变的发病机制以炎症细胞的激活和炎症细胞因子的产生为特征。众所周知，腺苷A（2A）受体激动剂具有抗炎作用，但这些化合物对胃粘膜病变发展的影响尚未见报道。本研究研究了一种强效选择性腺苷a （2A）受体激动剂ATL-146e对水浸应激和阿司匹林诱导的胃粘膜病变的影响。大鼠受到水浸应激，并通过单次腹腔注射腺苷a （2A）受体的强效和选择性激动剂给予阿司匹林，有或没有预处理。测定胃中髓过氧化物酶（MPO）浓度（作为中性粒细胞积累的指标）和促炎细胞因子、肿瘤坏死因子- α (tnf - α)和白细胞介素-1 β (il -1 β)。ATL-146e预处理能显著抑制应激和非甾体抗炎药引起的胃损伤。ATL-146e使胃中MPO、tnf - α和il -1 β含量均降至接近正常水平。一种特殊的腺苷A（2A）激动剂抑制胃炎症和损伤。A（2A）激动剂化合物可能对预防溃疡有用，并通过阻断胃炎症起作用。

Activation of adenosine A(2A) receptors reduces the production of various pro-inflammatory cytokines and suppresses neutrophil activation. Water-immersion restraint and aspirin are well known to cause gastric mucosal lesions. The pathogenesis of gastric mucosal lesions is characterized by activation of inflammatory cells and production of inflammatory cytokines. Agonists of adenosine A(2A) receptors are known to be anti-inflammatory, but the effects of these compounds on the development of gastric mucosal lesions has not been reported. In the present study, the effect of a potent and selective adenosine A(2A) receptor agonist, ATL-146e, on water-immersion stress-induced and aspirin induced gastric mucosal lesions were studied. Rats were subjected to water-immersion stress and administrated aspirin with or without pretreatment with a single intraperitoneal injection of a potent and selective agonist of the adenosine A(2A) receptor. The gastric concentrations of myeloperoxidase (MPO), as an index of neutrophil accumulation, and the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), were measured. The gastric lesions induced by stress and NSAIDs were significantly suppressed by pretreatment of ATL-146e. The gastric content of MPO, TNF-alpha and IL-1beta were all reduced to near normal levels by ATL-146e. A specific adenosine A(2A) agonist inhibits gastric inflammation and damage. A(2A) agonist compounds may be useful for preventing ulcers and appear to act by blocking gastric inflammation.