中文摘要：

目的 研究肠易激综合征（IBS）肠道树突细胞（DC）表型变化及细胞内丝裂原活化蛋白激酶（MAPK）信号通路的变化,初步探讨ERK1/2通路在介导DC异常免疫应答中的可能作用机制.方法 以母幼分离联合结直肠扩张刺激建立SD大鼠IBS模型（模型组,10只）,10只健康SD大鼠作为对照（对照组,10只）,以腹部收缩反射（AWR）实验评估大鼠内脏敏感性,造模成功后采用磁珠分选技术分离肠系膜淋巴结树突细胞（MLNDC）,流式检测其分选纯度及对照组大鼠表面主要组织相容性复合体Ⅱ（MHC-Ⅱ）类分子的表达,Western印迹法检测对照组及IBS组大鼠MLNDC中MHC-Ⅱ、磷酸化p38丝裂原激活蛋白激酶（p-p38）、p38丝裂原激活蛋白激酶（p38）、磷酸化细胞外调节蛋白激酶（p-ERK1/2）、细胞外调节蛋白激酶（ERK1/2）、磷酸化c-Jun氨基末端激酶（p-JNK）、c-Jun氨基末端激酶（JNK）的表达情况.结果 IBS组大鼠内脏敏感性显著高于对照组.流式细胞术检测磁珠分选后大鼠DC特异性抗原OX62＋ MLNDC为85.57％±7.67％.对照组大鼠MLNDC表面高表达MHC-Ⅱ类分子;与对照组相比,IBS组大鼠MLNDC表达MHC-Ⅱ类分子升高（1.05±0.13比0.67 ±0.18,t=-2.973,P=0.041）,同时,p-ERK的表达水平明显升高（3.21±0.48比2.34±0.85,江-3.130,P=0.035）,而p-JNK及p-p38的表达水平与对照组相比,差异无统计学意义（0.95±0.17比0.76±0.36,t=0.808,P=0.464;1.07±1.13比1.19±0.91,t=0.137,P=0.897）.结论 IBS大鼠肠道DC上调表达MHC-Ⅱ类分子,其可能与细胞内ERK1/2信号通路的活化有关.

英文摘要：

Objective To study the phenotypic alteration of intestinal dendritic cells （DC） in a rat model of irritable bowel syndrome （IBS） and the change of mitogen-activated protein kinase （MAPK） signaling pathway,in order to explore the potential mechanism of ERK1/2 pathway mediation in abnormal DC immune response.Methods IBS rat model was established by combining neonatal maternal separation and colorectal distension in 10 SD rats,and 10 healthy rats served as controls.Visceral sensitivity was evaluated with abdominal withdrawal reflex （AWR）.Mesenteric lymph node DC （MLNDC） was isolated and purified by magnetic label-based technique after modeling.Expression of surface major histocompatibility complex （MHC）-lⅡ in control rats was determined by flow cytometric analyses.Western-blot was used to determine the expression of MHC-]Ⅱ,p-p38,p38,phosphorylated extracellular regulated protein kinase （p-ERK1/2）,ERK1/2,phosphorylated c-Jun N-terminal kinase （p-JNK）,and JNK in MLNDC.Results Visceral sensitivity was significantly higher in the IBS group than in the control group.The purity of the OX62 positivity MLNDC following magnetic sorting was about 85.57% ± 7.67%.MLNDC in the control group expressed high level of MHC-Ⅱ.The expression of MHC-Ⅱ and p-ERK1/2 in MLNDC in the IBS group were higher than those in the control group （1.05 ± 0.13 vs 0.67 ± 0.18,t =-2.973,P =0.041;3.21 ± 0.48 vs 2.34 ± 0.85,t =-3.130,P =0.035）;while there was no significant difference in the expressions of p-JNK and p-p38 compared with the control groups （0.95 ± 0.17 vs 0.76 ± 0.36,t =0.808,P =0.464;1.07 ± 1.13 vs 1.19 ± 0.91,t =0.137,P =0.897）.Conclusion The intestinal DC in IBS rats show a upregulated expression of MHC-Ⅱ,which may be related to the activation of intracellular ERK1/2 pathway.