Attenuation of acute experimental colitis by preventing NPYY1 receptor signaling
Attenuation of acute experimental colitis by preventing NPYY1 receptor signaling
复制标题
DOI：
10.1152/ajpgi.00182.2004
复制
发表时间：
2005-03-01
影响因子：
4.5
通讯作者：
Ernfors, P
中科院分区：
文献类型：
--
作者：
Hassani, H;Lucas, G;Ernfors, P
神经肽 Y (NPY) 是一种 36 个氨基酸的肽，广泛表达于中枢和周围神经系统。 NPY 参与多种生理过程的调节，包括能量平衡、食物摄入和伤害感受。最近，我们发现皮肤神经源性炎症需要激活 NPY Y1 受体。由于神经源性炎症可能参与结肠炎，因此本研究的目的是使用遗传缺陷 NPY Y1 受体的小鼠研究 NPY Y1 受体在急性结肠炎中的作用。此外，还研究了Y1受体拮抗剂H409/22。动物接受 5% 葡聚糖硫酸钠 (DSS) 的饮用水，为期 7 天。一组动物还接受 Y1 受体拮抗剂，每天两次腹腔内给药。每天评估所有组的疾病活动性，持续 7 天。 DSS 在所有动物中诱发结肠炎，导致体重减轻、腹泻、上皮损伤、隐窝缩短和炎症浸润。然而，在 Y1 缺失突变小鼠以及接受 Y1 拮抗剂的小鼠中，该疾病的临床表现明显减弱。组织学分析表明，Y1 缺陷动物的组织损伤和溃疡较轻。与临床和组织学数据一致，与治疗的野生型动物相比，Y1 无效突变动物肠道中辣椒素诱导的血浆外渗显着减少。这些数据表明NPY和Y1受体参与肠道炎症，并表明抑制NPY Y1受体信号传导可能为治疗结肠炎症提供新的治疗方法。
Neuropeptide Y (NPY), a 36-amino acid peptide, is widely expressed in the central and peripheral nervous system. NPY is involved in the regulation of several physiological processes, including energy balance, food intake, and nociception. Recently, we showed that activation of the NPY Y1 receptor is required for cutaneous neurogenic inflammation. Because neurogenic inflammation could participate in colitis, the aim of this study was to investigate the role of the NPY Y1 receptor in acute colitis using mice genetically deficient of NPY Y1 receptor. In addition, the Y1 receptor antagonist H409/22, was also investigated. Animals received 5% dextran sulfate sodium (DSS) in drinking water for 7 days. One group of animals also received the Y1 receptor antagonist, administered intraperitoneally twice daily. Disease activity was assessed daily for 7 days in all groups. DSS induced colitis in all animals resulting in weight loss, diarrhea, epithelial damage, crypt shortening, and inflammatory infiltration. However, clinical manifestation of the disease was markedly attenuated in Y1 null mutant mice as well as in mice receiving the Y1 antagonist. Histological analysis showed that tissue damage and ulceration were less severe in Y1-deficient animals. Consistent with the clinical and histological data, capsaicin-induced plasma extravasation was significantly reduced in the gut of Y1 null mutant animals compared with treated wild-type animals. These data indicate that NPY and Y1 receptor are involved in intestinal inflammation and suggest that inhibition of NPY Y1 receptor signaling may provide a novel therapeutic approach in the treatment of colonic inflammation.