目的: 利用速激肽受体2（tachykinin receptor 2,Tacr2）基因敲除小鼠及诱导溃疡性结肠炎（ulcerative colitis,UC）小鼠模型,探讨Tacr2在小鼠UC发生、发展中的作用。方法: 小鼠按照基因型分成野生型组和基因敲除（纯合子）组,再按照给药与否进一步分成野生型造模组、纯合子造模组、野生型空白组、纯合子空白组。给造模组小鼠口服右旋葡聚糖硫酸钠（dextran sodium sulfate, DSS）构建UC小鼠模型,观察其UC活动指数及结肠组织中病理学改变、炎症因子及上游转录因子核因子NF-κB（nuclear factor-kappa B,NF-κB）的变化。结果: Tacr2基因敲除的纯合子小鼠经DSS诱导的UC症状比野生型造模组小鼠明显加重。进一步分析基础状态下结肠的免疫活性,发现在基础状态下,纯合子小鼠与野生型小鼠相比,结肠免疫活性明显降低,表现为结肠黏膜中 IL-1β、TNF-α、IL-6和NF-κB水平降低。结论: Tacr2对UC的发生、发展有抑制作用。
Objective: Using Tacr2(tachykinin receptor 2) gene knockout mice and induction of ulcerative colitis (UC) to study the influence and mechanism of Tacr2 on development of ulcerative colitis(UC). Methods Tacr2 knockout mice and wild type mice were treated with oral dextran sodium sulfate（DSS）solution for a week to induce UC, non-treated Tacr2 knockout mice and wild type mice were served as blank controls. Activity index and pathological change of colonic mucosa were studied, and the inflammation score, NF-κB expression in colonic tissue were detected. Results Tacr2 knockout mice showed higher susceptibility to DSS solution. When compared with wild type mice, Tacr2 knockout mice had a significantly decreased level of immunocompetence, presenting with decreased levels of IL-1β, TNF-α, IL-6 and NF-κB. Conclusions Tacr2 has an inhibitory effect on the development of ulcerative colitis in mice.
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