Colonic mucosal N-methyl-D-aspartate receptor mediated visceral hypersensitivity in a mouse model of irritable bowel syndrome
Colonic mucosal N-methyl-D-aspartate receptor mediated visceral hypersensitivity in a mouse model of irritable bowel syndrome
复制标题
肠易激综合征小鼠模型中结肠粘膜 N-甲基-D-天冬氨酸受体介导的内脏超敏反应
DOI：
10.1111/1751-2980.12374
复制
发表时间：
2016-07-01
影响因子：
3.5
通讯作者：
Zuo, Xiu Li
中科院分区：
文献类型：
--
作者：
Qi, Qing Qing;Chen, Fei Xue;Zuo, Xiu Li
目的探讨肠易激综合征（IBS）患者结肠黏膜n -甲基- d -天冬氨酸受体（NMDAR）是否参与内脏超敏反应。方法采用三硝基苯磺酸（TNBS）腹腔注射sc57bl /6小鼠，建立ibs样内脏超敏模型。接受等量50%乙醇的人作为对照。腹部戒断反射（AWR）评分对结肠直肠膨胀（CRD）的反应被用来评估内脏敏感性。免疫组化和Western blot检测结肠黏膜NMDAR水平。测定小鼠粪便中谷氨酸和氨的浓度。记录结肠内给药氨或NMDAR拮抗剂后内脏敏感性的变化。结果建立的肠易激样内脏超敏小鼠模型结肠无明显炎症反应。ibs样小鼠结肠黏膜NMDAR水平显著高于对照组，且与AWR评分呈正相关。tnbs处理小鼠粪便中的谷氨酸水平与对照组相似，但氨水平明显高于对照组。经NMDAR拮抗剂MK801预处理后，结肠内给药氨可诱导小鼠内脏超敏反应。结论结肠黏膜NMDAR过表达可能参与肠易激综合征内脏超敏反应的发生。我们的研究确定了结肠腔内氨对结肠黏膜NMDAR的影响，这是治疗IBS的一种潜在的新的靶向机制。
ObjectiveThe aim of this study was to investigate whether colonic mucosal N-methyl-D-aspartate receptor (NMDAR) participates in visceral hypersensitivity in irritable bowel syndrome (IBS).MethodsC57BL/6 mice were administered intrarectally with trinitrobenzenesulfonic acid (TNBS) for the establishment of an IBS-like visceral hypersensitivity model. Those received an equivalent volume of 50% ethanol were regarded as the controls. Abdominal withdrawal reflex (AWR) scores in response to colorectal distention (CRD) were used to assess visceral sensitivity. NMDAR levels in the colonic mucosa were detected by both immunohistochemistry and Western blot. The concentrations of glutamate and ammonia in the feces of the mice were measured. Changes in visceral sensitivity after the intracolonic administration of ammonia or NMDAR antagonist were recorded.ResultsThe established IBS-like mouse model of visceral hypersensitivity showed no evident inflammation in the colon. NMDAR levels in the colonic mucosa of the IBS-like mice were significantly higher compared with the controls, and were positively associated with AWR scores. The glutamate level in the feces of the TNBS-treated mice was similar to that of the controls, although the ammonia level was significantly higher. Intracolonic administration of ammonia induced visceral hypersensitivity in mice, which was repressed by pretreatment with NMDAR antagonist MK801.ConclusionsOverexpressed NMDAR in the colonic mucosa may participate in the pathogenesis of visceral hypersensitivity in IBS. Our study identifies the effect of ammonia in the colonic lumen on NMDAR in the colonic mucosa as a potential novel targeted mechanism for IBS treatment.