The adenosine A3 receptor agonist, N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide, is protective in two murine models of colitis
The adenosine A3 receptor agonist, N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide, is protective in two murine models of colitis
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DOI：
10.1016/s0014-2999(03)01570-x
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发表时间：
2003-04-18
影响因子：
5
通讯作者：
Szabó, C
中科院分区：
文献类型：
--
作者：
Mabley, J;Soriano, F;Szabó, C
本研究评价了腺苷A(3)受体激动剂N-6-(3-iodobenzyl)-adenosine-5‘-N-methyluronamide(IB-MECA)在两种结肠炎小鼠模型中的作用，即葡聚糖硫酸钠诱导的结肠炎和白细胞介素10基因缺陷小鼠的自发性结肠炎。IB-MECA每天口服两次，剂量分别为1或3 mg/kg/d。通过大体(体重、直肠出血)和生化(结肠髓过氧化物酶、丙二醛、趋化因子和细胞因子水平)来评估结肠损伤和炎症。在葡聚糖硫酸钠诱导的结肠炎和10周大的interieukin-10(-/-)小鼠中，随着细胞因子和趋化因子水平的增加，结肠炎性细胞浸润显著增加，随后发生与自由基相关的损伤。IB-MECA对结肠炎诱导的炎性细胞浸润和损伤均有保护作用，并能减轻结肠炎性细胞因子和趋化因子水平的升高。因此，激活腺苷A(3)受体在预防结肠炎方面是有效的。(C)2003爱思唯尔科学公司保留所有权利。
This study evaluated the effects of the adenosine A(3) receptor agonist, N-6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA), in two murine models of colitis, the dextran sodium sulphate-induced colitis and the spontaneous colitis found in interleukin-10 gene deficient mice. IB-MECA was given orally twice a day at a dose of either 1 or 3 mg/kg/day. Evaluation of colon damage and inflammation was determined grossly (body weight, rectal bleeding) and biochemically (colon levels of myeloperoxidase, malondialdehyde, chemokines and cytokines). There was significantly increased inflammatory cell infiltration into the colon associated with an increase in colon levels of cytokines and chemokines; with subsequent free radical related damage in both dextran sodium sulphate-induced colitis and 10-week-old interieukin-10(-/-) mice. IB-MECA protected in both models against the colitis induced inflammatory cell infiltration and damage and attenuated the increases in colon inflammatory cytokine and chemokine levels. Thus activation of the adenosine A(3) receptor is effective in protecting against colitis. (C) 2003 Elsevier Science B.V All rights reserved.