目的观察阻断小胶质细胞的MAPK-p38信号通路对肠易激综合征(intestinal bowel syndrome,IBS)大鼠内脏敏感性的影响,为探讨IBS内脏敏化的神经机制提供理论依据。方法 30只昆明鼠用旋毛虫灌胃的方法成功制作IBS模型,随机分为Ⅰ和Ⅱ两个大组,各组再随机分为3个亚组:生理盐水IBS对照组、单纯IBS组、SB203580组,每组5只。IBS大鼠通过脊髓插管给予小胶质细胞信号转导途径MAPK-p38的特异性阻断剂SB203580干预小胶质细胞的功能。Ⅰ组用于观察痛行为学积分、腹直肌肌电以及小胶质细胞活化情况。Ⅱ组再取5只大鼠作为空白对照组,用于测定骶髓DCN单位放电。结果 SB203580组的痛行为学积分、腹直肌肌电反应变化(频率、振幅)和小胶质细胞活化程度OD值显著低于脊髓插管给予生理盐水IBS对照组、单纯IBS组(P〈0.05)。脊髓插管给予SB203580组DCN的单位放电频率显著低于脊髓插管给予生理盐水IBS对照组、单纯IBS组(P〈0.05),但高于空白对照组DCN的单位放电频率,差异有统计学意义(P〈0.05)。结论小胶质细胞参与了IBS大鼠的内脏敏化反应,当其细胞信号转导途径被阻断,即可明显阻断后续疼痛反应的发生,提示小胶质细胞在IBS内脏敏化中发挥重要作用,该反应可能是通过细胞信号转导途径P38实现的。
Objective To explore the mechanism of hyperagesia of rats with IBS by investigating the influence of SB203580(inhibitor of MAPK-p38) on the microglia cells activation. Methods Thirty rats were gavaged with Trichinella spiralis to establish the IBS model,and then randomized into 2 groups.The rats in 2 groups were respectively randomly assigned into 3 subgroups:normal saline IBS group,SB203580 group,and IBS group.SB203580 and normal saline were given through spinal cord intubation.The rats in one group were used to observe the behavioral pain assessment scale,the changes of electroactivity of the rectus abdominis and the microglia cells activation in dorsal commissural nucleus(DCN).The rats in the other group were used to detect the unit discharge of DCN with the blank rats as controls. Results The behavioral pain scale,frequency and amplitude of rectus abdominis EMG and OD of the microglia cells activation in SB203580 group were significantly lower than those in the other two groups(P0.05).The unit discharge of DCN were significantly lower in SB203580 group than those in normal saline IBS group and IBS group(P0.05),but significantly higher than in blank control group(P0.05). Conclusion The results suggest that the microglia cells may play an important role in the hyperagesia of IBS rats through MAPK-p38 signaling pathway.