De Schepper H U, De Man J G, Van Nassauw L, Timmermans J-P, Herman A G, Pelckmans P A, De Winter B Y
Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
Gut. 2007 Feb;56(2):195-202. doi: 10.1136/gut.2006.104745. Epub 2006 Sep 14.
Patients with inflammatory bowel disease often present with abnormal gut motility away from the inflammatory site. We studied remote motility disturbances and their pathophysiology in a rat model of colitis.
Colitis was induced 72 h prior to experiments using trinitrobenzene sulphate (TNBS) instillation. Inflammation was verified using histology and myeloperoxidase (MPO) measurements. To assess gut motility, we determined gastric emptying, distal front and geometric centre (GC) of intestinal transit 30 min after intragastric administration of a semiliquid Evans blue solution. The effects of hexamethonium (20 mg/kg), capsaicin (125 mg/kg) and pelvic nerve section on colitis induced motility changes were evaluated. c-Fos expression was studied in the pelvic nerve dorsal root ganglion (DRG) S1.
Colitis reduced gastric emptying from 38.4 (3.6)% in controls to 22.7 (4.4)% in TNBS treated rats in the absence of local gastric inflammation. Colitis had no effect on the distal front or on the geometric centre of small intestinal transit. Hexamethonium reduced gastric emptying in controls to 26.3 (4.1)% but restored it to 35.8 (4.4)% in TNBS treated rats. Capsaicin significantly impaired gastric emptying in controls from 33.1 (5.2)% to 9.5 (3.3)% while this effect was less pronounced in TNBS treated rats (from 19.2 (2.3)% to 11.5 (3.8)%; NS). In TNBS treated rats, pelvic nerve section completely restored gastric emptying from 19.8 (5.3)% to 52.5 (6.3)% without any effect on gastric emptying in control rats. TNBS colitis induced de novo c-Fos expression in the DRG S1.
Experimental colitis in rats delays gastric emptying via a neuronal pathway involving pelvic afferent nerve hyperactivity.
炎症性肠病患者常出现远离炎症部位的肠道运动异常。我们在大鼠结肠炎模型中研究了远隔部位的运动障碍及其病理生理学机制。
在实验前72小时，通过灌注三硝基苯磺酸（TNBS）诱导大鼠发生结肠炎。通过组织学检查和髓过氧化物酶（MPO）测定来验证炎症情况。为评估肠道运动，在胃内给予半液体伊文思蓝溶液30分钟后，我们测定了胃排空、小肠传输的远端前沿及几何中心（GC）。评估了六甲铵（20mg/kg）、辣椒素（125mg/kg）及盆神经切断对结肠炎诱导的运动变化的影响。研究了盆神经背根神经节（DRG）S1中c-Fos的表达。
在无局部胃炎症的情况下，结肠炎使胃排空率从对照组的38.4（3.6）%降至TNBS处理大鼠的22.7（4.4）%。结肠炎对小肠传输的远端前沿或几何中心无影响。六甲铵使对照组的胃排空率降至26.3（4.1）%，但在TNBS处理的大鼠中使其恢复至35.8（4.4）%。辣椒素使对照组的胃排空率从33.1（5.2）%显著降低至9.5（3.3）%，而在TNBS处理的大鼠中这种作用不那么明显（从19.2（2.3）%降至11.5（3.8）%；无统计学差异）。在TNBS处理的大鼠中，盆神经切断使胃排空率从19.8（5.3）%完全恢复至52.5（6.3）%，而对对照组大鼠的胃排空无影响。TNBS诱导的结肠炎使DRG S1中出现了新的c-Fos表达。
大鼠实验性结肠炎通过涉及盆传入神经活动亢进的神经通路延迟胃排空。
