Katada K, Yoshida N, Suzuki T, Okuda T, Mizushima K, Takagi T, Ichikawa H, Naito Y, Cepinskas G, Yoshikawa T
Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
Inflamm Res. 2008 Feb;57(2):84-91. doi: 10.1007/s00011-007-7098-y.
Angiotensin II (Ang II) receptor blockers have been reported to contribute to cytoprotective effects in various organs. However, the role of renin-angiotensin system (RAS) in modulation of the inflammatory bowel disease (IBD) remains unclear. In this study we assessed the role of angiotensin II type 1a (AT1a) receptor on the outcome of dextran sulfate sodium (DSS)-induced acute colitis by employing AT1a receptor deficient mice.
The acute colitis was induced in wild type (WT) and AT1a receptor deficient mice by giving orally 3% DSS in drinking water for 7 days.
Induction of DSS colitis resulted in up-regulation of Ang II and AT1a receptor in the colonic mucosa of WT mice. In parallel, loss of body weight, an increase in disease activity index (DAI), and the shortening of colon were found in DSS-challenged WT mice. In addition, an increase in thiobarbituric acid (TBA)-reactive substances and myeloperoxidase (MPO) activity, along with the up-regulation of tumor necrosis factor (TNF)-alpha were detected in the colonic mucosa of DSS-challenged WT mice. The endpoints mentioned above were significantly ameliorated in DSS-challenged AT1a receptor deficient mice.
RAS is involved in the pathophysiology of DSS-induced colitis and AT1a receptor may be a novel therapeutic target for the treatment of IBD.
据报道，血管紧张素II（Ang II）受体阻滞剂对多种器官具有细胞保护作用。然而，肾素-血管紧张素系统（RAS）在炎症性肠病（IBD）调节中的作用仍不清楚。在本研究中，我们通过使用AT1a受体缺陷小鼠评估了1a型血管紧张素II（AT1a）受体在葡聚糖硫酸钠（DSS）诱导的急性结肠炎转归中的作用。
通过给野生型（WT）和AT1a受体缺陷小鼠口服含3% DSS的饮用水7天来诱导急性结肠炎。
DSS结肠炎的诱导导致WT小鼠结肠黏膜中Ang II和AT1a受体上调。同时，在接受DSS刺激的WT小鼠中发现体重减轻、疾病活动指数（DAI）增加以及结肠缩短。此外，在接受DSS刺激的WT小鼠结肠黏膜中检测到硫代巴比妥酸（TBA）反应性物质和髓过氧化物酶（MPO）活性增加，以及肿瘤坏死因子（TNF）-α上调。上述终点在接受DSS刺激的AT1a受体缺陷小鼠中得到显著改善。
RAS参与DSS诱导的结肠炎的病理生理学过程，AT1a受体可能是治疗IBD的新治疗靶点。
