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

腺苷A(2A)受体的激活减少了各种促炎细胞因子的产生，并抑制了中性粒细胞的激活。众所周知，浸水束缚和阿司匹林会导致胃粘膜损伤。胃粘膜病变的发病机制以炎症细胞的激活和炎性细胞因子的产生为特征。腺苷A(2A)受体激动剂已知具有抗炎作用，但这些化合物对胃粘膜病变发展的影响尚未见报道。本文研究了腺苷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损伤的影响。大鼠受到水浸泡应激，并给予阿司匹林，无论有没有预处理，只需一次腹腔注射一种有效和选择性的腺苷A(2A)受体激动剂。测定胃中性粒细胞聚集的指标髓过氧化物酶(MPO)和促炎细胞因子肿瘤坏死因子-α(TNF-α)和白介素1-β(IL-1β)。ATL-146E可显著抑制应激和非甾体抗炎药所致的胃损伤。ATL-146E可使胃液中MPO、TNF-α和IL-1β含量降至接近正常水平。一种特定的腺苷A(2A)激动剂可抑制胃部炎症和损伤。A(2A)激动剂化合物可能有助于预防溃疡，并似乎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.