目的探讨MAPK-P38特异性抑制剂SB203580对肠易激综合征(irritable bowel syndrome,IBS)大鼠后连合核(dorsalcommissural nucleus,DCN)中促分裂素原活化蛋白激酶(mitogen-activated protein kinases,MAPKase)信号通路细胞因子的影响,为研究IBS内脏敏化提供理论依据。方法 10只正常大鼠随机分为2组:正常对照组(A组,n=5)、正常结肠扩张刺激组(B组,n=5);另15只IBS大鼠随机分为3组:IBS组(C组,n=5)、IBS结肠扩张刺激组(D组,n=5)、抑制剂组(E组,n=5)。给予B、D、E组结肠扩张刺激,另外给予E组大鼠椎管内注射抑制剂SB203580。采用免疫荧光组织化学及电生理方法观察大鼠DCN中MAPKase信号通路细胞因子P38、ERK表达及腹直肌肌电的变化。结果与IBS扩张刺激组比较,抑制剂组P38表达明显下降(P〈0.01),ERK表达亦明显下降(P〈0.05),与正常对照组大鼠对比无显著差异(P〉0.05)。结论 IBS大鼠内脏敏化与DCN中的MAPK信号转导途径密切相关,内脏敏化的完成可能是通过该途径实现的。
Objective To explore the effects of SB203580 on the MAPK-p38 in dorsal commissural nucleus(DCN) of irritable bowel syndrome(IBS)rats,and to provide a theoretical evidence for studying the visceral hypersensitivity in IBS.Methods Ten SD male rats were randomized into 2 groups:control group(group A,n=5)and colorectal distention group(group B,n=5).Fifteen IBS rats were randomly assigned into 3 groups:IBS group(group C,n=5),IBS colorectal distention group(group D,n=5),inhibitor group(group E,n=5).The rats in groups B,D,E were given the stimulation of colorectal distention,and the rats in group E was additionally epidurally injected with SB203580.Immunofluorescent staining and electrophysiology method were used to observe the expression of P38 and ERK and myoelectricity of rectus abdominis in DCN of rats.Results The expression of P38 in group E was significantly lower than those in group D(P0.01),and the expression of ERK was also lower(P0.05).There was no significant difference in expression of P38 and ERK between group E and group A(P0.05).Conclusion The MAPK signaling in DCN is involved in visceral hypersensitivity in IBS rats.