Berdún S, Rychter J, Vergara P
Department of Cell Biology, Physiology and Immunology, Veterinary School, Universitat Autònoma de Barcelona, Barcelona, Spain.
Neuroscience Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
Neurogastroenterol Motil. 2016 Jun;28(6):816-26. doi: 10.1111/nmo.12777. Epub 2016 Feb 22.
Surgical handling of the bowel evokes degranulation of peritoneal mast cells (PMC). Nonetheless, role of PMCs in postoperative ileus (POI) is somewhat controversial. We aimed to investigate if intestinal manipulation elicits changes in afferent mediators related to MC activation and alteration of gastrointestinal (GI) motility.
Postoperative ileus was induced by intestinal manipulation in Sprague-Dawley rats. Additionally, compound 48/80 (C48/80) and ketotifen were used to modulate MC activity. Rat mast cell protease 6 (RMCP-6, ELISA) release was determined in peritoneal lavage 20 min after intestinal manipulation. At 24 h, GI transit was determined. Gene expression of calcitonin gene-related peptide (CGRP), protease-activated receptor-2 (PAR-2), nerve growth factor (NGF), and TrkA receptor was determined (PCR) in dorsal root ganglia (DRG). Ileal wall inflammation was assessed by myeloperoxidase (MPO) activity, interleukin-6 expression (IL-6).
Intestinal manipulation and exposure to C48/80-induced degranulation of PMCs delayed GI transit and up-regulated IL-6 and MPO activity. Intestinal manipulation, but not C48/80, up-regulated CGRP, PAR-2, and NGF/TrkA in DRGs. Ketotifen only improved gastric emptying and fecal output. Up-regulation of CGRP and TrkA expression in DRG was not prevented by ketotifen.
CONCLUSIONS & INFERENCES: Postoperative ileus is accompanied by activation of CGRP, NGF-TrkA, and PAR-2 in DRGs. Our results suggest that these mediators could be a target in further POI studies in order to find new therapeutic targets for this medical condition.
肠道手术操作可引起腹膜肥大细胞（PMC）脱颗粒。然而，PMC在术后肠梗阻（POI）中的作用存在一定争议。我们旨在研究肠道操作是否会引起与肥大细胞激活相关的传入介质变化以及胃肠（GI）动力改变。
通过对Sprague-Dawley大鼠进行肠道操作诱导术后肠梗阻。此外，使用化合物48/80（C48/80）和酮替芬来调节肥大细胞活性。在肠道操作后20分钟测定腹膜灌洗中大鼠肥大细胞蛋白酶6（RMCP-6，酶联免疫吸附测定）的释放。在24小时时，测定胃肠转运。在背根神经节（DRG）中测定降钙素基因相关肽（CGRP）、蛋白酶激活受体-2（PAR-2）、神经生长因子（NGF）和TrkA受体的基因表达（聚合酶链反应）。通过髓过氧化物酶（MPO）活性、白细胞介素-6表达（IL-6）评估回肠壁炎症。
肠道操作和暴露于C48/80诱导的PMC脱颗粒延迟了胃肠转运，并上调了IL-6和MPO活性。肠道操作而非C48/80上调了DRG中的CGRP、PAR-2和NGF/TrkA。酮替芬仅改善了胃排空和粪便排出量。酮替芬不能阻止DRG中CGRP和TrkA表达的上调。
术后肠梗阻伴有DRG中CGRP、NGF-TrkA和PAR-2的激活。我们的结果表明，这些介质可能是进一步进行POI研究的靶点，以便为这种疾病找到新的治疗靶点。
