Ravnefjord Anna, Pettersson Madeleine, Rehnström Erika, Martinez Vicente
AstraZeneca R&D Mölndal, Mölndal, Sweden.
Int J Exp Pathol. 2008 Dec;89(6):476-89. doi: 10.1111/j.1365-2613.2008.00623.x.
Colonic ischaemia and mast cells have been involved in the pathophysiology of the functional gastrointestinal disorder irritable bowel syndrome, although the cause-effect relationships remain unknown. We assessed long-term histopathological and functional changes associated to an acute ischaemic episode (1 h) of the colon, followed by 8-week recovery, in rats. Functional colonic alterations [sensitivity during colorectal distension (CRD), compliance and propulsive motility] were assessed regularly during the recovery. Colonic histopathology (presence of inflammation, morphometric alterations and variations in neuronal density in the enteric nervous system) 8-week postischaemia was assessed. Following ischaemia, none of the functional parameters tested (motility, sensitivity and compliance) were affected. At necropsy, the colon presented an overall normal appearance with an increase in weight of the ischaemic area (mg/cm: 99 +/- 6; P < 0.05 vs. control: 81 +/- 4 or sham ischaemia: 81 +/- 3). Histopathological evaluations revealed the presence of a local infiltrate of mast cells in the area of ischaemia (nb of mast cells: 142 +/- 50; P < 0.05 vs. control, 31 +/- 14 or sham ischaemia: 40 +/- 16), without other significant alterations. Animals subjected to colonic ischaemia and treated 8 weeks later with the mast cell degranulator, compound 48/80, showed no changes in CRD-related pain responses. These studies show that acute colonic ischaemia is associated with the presence of a long-term local infiltration of mast cells, located within the serosa and muscle layers, despite the absence of functional changes, including colonic sensitivity. Considering the important pathophysiological functions of mast cells, the observed mast cell infiltration may be involved in ischaemia-induced functional changes yet to be characterized.
结肠缺血和肥大细胞参与了功能性胃肠疾病肠易激综合征的病理生理过程,尽管因果关系尚不清楚。我们评估了大鼠结肠急性缺血发作(1小时)后8周恢复过程中与之相关的长期组织病理学和功能变化。在恢复过程中定期评估结肠功能改变[结肠扩张时的敏感性(CRD)、顺应性和推进性运动]。评估缺血后8周的结肠组织病理学(炎症的存在、形态计量学改变和肠神经系统中神经元密度的变化)。缺血后,所测试的功能参数(运动性、敏感性和顺应性)均未受影响。尸检时,结肠外观总体正常,但缺血区域重量增加(mg/cm:99±6;与对照组81±4或假缺血组81±3相比,P<0.05)。组织病理学评估显示缺血区域存在肥大细胞局部浸润(肥大细胞数量:142±50;与对照组31±14或假缺血组40±16相比,P<0.05),无其他显著改变。接受结肠缺血并在8周后用肥大细胞脱颗粒剂化合物48/80治疗的动物,CRD相关疼痛反应无变化。这些研究表明,急性结肠缺血与浆膜层和肌肉层内长期存在的肥大细胞局部浸润有关,尽管没有包括结肠敏感性在内的功能变化。考虑到肥大细胞重要的病理生理功能,观察到的肥大细胞浸润可能参与了缺血诱导的尚未明确的功能变化。