Cajal间质细胞对肠易激综合征大鼠内脏敏化的作用及机制

Role and action mechanism of interstitial cells of Cajal in visceral sensitization in rats with irritable bowel syndrome

目的探讨Cajal间质细胞(ICC)对肠易激综合征(IBS)内脏敏化的作用及其可能机制。方法采用母乳鼠分离方法构建IBS大鼠模型。实验分为正常对照组(A组)、结肠扩张组(B组)、IBS模型组(C组)、IBS结肠扩张组(D组)、IBS结肠扩张+甲磺酸伊马替尼(STI-571)组[E组,腹腔注射STI-571 0.5ml/(kg·d),连续5d]、IBS结肠扩张+色甘酸钠(DC)组[F组,腹腔注射DC 20mg/(kg·d),连续5d]和结肠扩张+STI-571+DC组(G组,腹腔同时注射STI-571和DC)7组,每组10只。采用免疫荧光组织化学及电生理学方法观察各组大鼠肠道ICC活化、腹直肌肌电和骶髓后连合核(DCN)放电频率的变化。结果 IBS大鼠腹直肌以及DCN放电频率和幅度均高于正常大鼠(P<0.05);结肠扩张刺激进一步提高了正常大鼠和IBS大鼠腹直肌和DCN的放电频率,但对IBS大鼠的作用更为明显(P<0.05);肥大细胞膜稳定剂DC未能有效阻断结肠扩张刺激诱发的IBS大鼠腹直肌和DCN放电频率增高(P>0.05);采用STI-571抑制ICC增殖,可明显抑制结肠扩张刺激诱发的IBS大鼠腹直肌和DCN放电频率增高(P<0.05)。IBS大鼠胃肠道ICC密度高于正常大鼠(P<0.05);DC对ICC增殖活化无影响,而STI-571可有效抑制ICC的增殖活化。结论 ICC与IBS大鼠内脏敏化关系密切,而肥大细胞在IBS内脏敏化中的作用较弱。

Objective To explore the role and action mechanism of interstitial cells of Cajal （ICC） in the visceral sensitization of rats with irritable bowel syndrome （IBS）. Methods The experimental rats were divided into 7 groups （10 each）, including normal group, normal group with colonic expansion, IBS group, IBS group with colonic expansion, IBS group with colonic expansion and receiving STI-571, IBS group with colonic expansion and receiving DC, IBS group with colonic expansion and receiving both STL571 and STI-571. Immunofluorescent double staining and electrophysiological method were used to observe the activity of ICC, the electroactivity of the rectus abdominis and the discharge frequency in dorsal commissural nucleus （DCN）. Results The discharge frequency and amplitude of the rectus abdominis and D CN in the IBS rats were higher than those in the normal rats （P〈0.05）. Colonic expansion could further increase the discharge frequency of the rectus abdominis and DCN in the normal rats and IBS rats, but it was more effective in the IBS rats （P〈0.05）. DC could not effectively reduce the discharge frequency of the rectus abdominis and DCN induced by colonic expansion in the IBS rats （P〉0.05）. After inhibiting ICC proliferation with STI-571, the discharge of the rectus abdominis and DCN in the IBS rats induced by colonic expansion was significantly inhibited （P〈0.05）. The ICC density in gastrointestinal tract of the IBS rats was higher than that in the normal rats （P〈0.05）; DCs had no effect on ICC proliferation and activation, while STI-571 could effectively inhibit ICC proliferation and activation. Conclusion IBS visceral sensitization is closely related to ICC, while mast cells play a weak role in IBS visceral sensitization.