Vanilloid receptor (TRPV1)-deficient mice show increased susceptibility to dinitrobenzene sulfonic acid induced colitis
Vanilloid receptor (TRPV1)-deficient mice show increased susceptibility to dinitrobenzene sulfonic acid induced colitis
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DOI：
10.1007/s00109-005-0016-2
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发表时间：
2006-02-01
影响因子：
4.7
通讯作者：
Lutz, B
中科院分区：
文献类型：
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作者：
Massa, F;Sibaev, A;Lutz, B
在人类结肠中，香草素受体TRPV 1在炎症期间在传入神经末梢和上皮细胞中都过表达。在过去的几年中，使用TRPV 1激动剂和拮抗剂的药理学实验表明，TRPV 1受体可能在胃肠道中发挥促炎和保护作用。在这里，我们应用遗传学方法来定义TRPV 1的作用，并分析了TRPV 1缺陷（TRPV 1（-/-））小鼠中二硝基苯磺酸（DNBS）诱导的结肠炎的影响。与野生型同窝小鼠（TRPV 1（+/+））相比，直肠内输注DNBS诱导TRPV 1（-/-）小鼠的炎症增加，如通过肉眼评分和髓过氧化物酶测定所评价。这一发现表明，TRPV 1受体是需要的保护内的感觉通路，调节结肠炎症启动后的反应。在DNBS处理后8和24 h进行的环形平滑肌细胞的电生理记录显示TRPV 1（-/-）结肠中有强烈的自发振荡动作电位，但TRPV 1（+/+）结肠中没有，表明TRPV 1早期介导的炎症诱导的平滑肌活动刺激的控制。这些意想不到的结果表明TRPV 1受体介导针对实验诱导的结肠炎症的内源性保护。
In the human colon, vanilloid receptor TRPV1 is overexpressed both in afferent nerve terminals and in epithelial cells during inflammation. In the past years, pharmacological experiments using TRPV1 agonists and antagonists revealed that TRPV1 receptors may play proinflammatory and protective roles in the gastrointestinal tract. Here, we applied a genetic approach to define the role of TRPV1 and analyzed the effects of dinitrobenzene sulfonic acid (DNBS)-induced colitis in TRPV1-deficient (TRPV1(-/-)) mice. Intrarectal infusion of DNBS induced increased inflammation in TRPV1(-/-) mice compared to wild-type littermates (TRPV1(+/+)) as evaluated by macroscopic scoring and myeloperoxidase assays. This finding indicates that TRPV1 receptors are required for the protection within sensory pathways that regulate the response following the initiation of colonic inflammation. Electrophysiological recordings from circular smooth-muscle cells, performed 8 and 24 h after DNBS treatment, revealed strong spontaneous oscillatory action potentials in TRPV1(-/-) but not in TRPV1(+/+) colons, indicating an early TRPV1-mediated control of inflammation-induced irritation of smooth-muscle activities. These unexpected results suggest that TRPV1 receptors mediate endogenous protection against experimentally induced colonic inflammation.