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

炎症性肠病动物模型分析及治疗应用

• 批准号: 15590617
• 负责人: WATANABE Sumio
• 金额: $ 2.18万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590617/
• 关键词: Adenosine; inflammatory cytokine; サイトカイン; サイクリックAMP

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.

腺苷A（2A）受体的激活减少各种促炎细胞因子的产生并抑制中性粒细胞活化。众所周知，水浸束缚和阿司匹林可引起胃粘膜病变。胃粘膜病变的发病机制以炎性细胞的活化和炎性细胞因子的产生为特征。已知腺苷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报道。在本研究中，一个有效的和选择性的腺苷A（2A）受体激动剂，ATL-146 e，对水浸应激和阿司匹林诱导的胃粘膜病变的影响进行了研究。将大鼠置于水浸应激状态下，给药阿司匹林，预先或不预先单次腹腔注射腺苷A（2A）受体的有效和选择性激动剂。测量胃内髓过氧化物酶（MPO）浓度（作为中性粒细胞蓄积的指标）以及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-146 e预处理可显著抑制应激和NSAID引起的胃损伤。ATL-146 e可使胃内MPO、TNF-α和IL-1 β含量降至接近正常水平。一种特异性腺苷A（2A）激动剂抑制胃炎症和损伤。A（2A）激动剂化合物可用于预防溃疡，并且似乎通过阻断胃炎症起作用。

项目成果

Specific type IV phosphodiesterase inhibitor ameliorates thioacetamide‐induced liver injury in rats

• DOI: 10.1111/j.1440-1746.2004.03512.x
• 发表时间: 2005-01
• 期刊: Journal of Gastroenterology and Hepatology
• 影响因子: 4.1
• 作者: T. Matsuhashi;M. Otaka;M. Odashima;M. Jin;K. Komatsu;Noriaki Konishi;Isao Wada;Toshihiro Sato;Y. Horikawa;Reina Ohba;Jinko Oyaké;Natsumi Hatakeyama;Sumio Watanabe

Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates indomethacin-induced gastric mucosal injury in rats.

咯利普兰是一种特定的 IV 型磷酸二酯酶抑制剂，可改善吲哚美辛引起的大鼠胃粘膜损伤。

• 发表时间: 2003
• 期刊: Pathophysiology. 9
• 作者: Nakamura C;Otaka M;Odashima M;Jin M;Konishi N;Horikawa Y;et al.
• 通讯作者: et al.

Selective adenosine A receptor agonist, ATL-146e, attenuates stress-induced gastric lesions in rats.

选择性腺苷 A 受体激动剂 ATL-146e 可减轻大鼠应激性胃损伤。

• 发表时间: 2005
• 期刊: J Gastroenterol Hepatol 20
• 作者: Odashima M;Otaka M;Jin M;Komatsu K;Wada I;Matsuhashi T;et al.
• 通讯作者: et al.

仲村智恵子, 大高道郎, 小田嶋傑, 神万里夫, 堀川洋平, 渡辺純夫: "Rolipram, a specific typeIV phosphodiesterase inhibitor, amelioprates in dpmethacin-induced gastric mucosal injury in rats"Pathophysiology. 9. 195-200 (2003)

Chieko Nakamura、Michio Otaka、Satoru Odashima、Mario Kami、Yohei Horikawa、Sumi Watanabe：“咯利普兰，一种特定的 IV 型磷酸二酯酶抑制剂，在 dpmethacin 诱导的大鼠胃粘膜损伤中发挥作用” 9. 195-200 (2003)。