Costes Léa M M, van der Vliet Jan, Farro Giovanna, Matteoli Gianluca, van Bree Sjoerd H W, Olivier Brenda J, Nolte Martijn A, Boeckxstaens Guy E, Cailotto Cathy
Tytgat Institute for Liver and Intestinal Research, Academic medical center (AMC), Amsterdam, The Netherlands.
Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Belgium.
PLoS One. 2014 Jul 10;9(7):e102211. doi: 10.1371/journal.pone.0102211. eCollection 2014.
Postoperative ileus is characterized by a transient impairment of the gastrointestinal motility after abdominal surgery. The intestinal inflammation, triggered by handling of the intestine, is the main factor responsible for the prolonged dysmotility of the gastrointestinal tract. Secondary lymphoid organs of the intestine were identified as essential components in the dissemination of inflammation to the entire gastrointestinal tract also called field effect. The involvement of the spleen, however, remains unclear.
In this study, we investigated whether the spleen responds to manipulation of the intestine and participates in the intestinal inflammation underlying postoperative ileus.
Mice underwent Laparotomy (L) or Laparotomy followed by Intestinal Manipulation (IM). Twenty-four hours later, intestinal and colonic inflammation was assessed by QPCR and measurement of the intestinal transit was performed. Analysis of homeostatic chemokines in the spleen was performed by QPCR and splenic cell populations analysed by Flow Cytometry. Blockade of the egress of cells from the spleen was performed by administration of the Sphingosine-1-phosphate receptor 1 (S1P1) agonist CYM-5442 10 h after L/IM.
A significant decrease in splenic weight and cellularity was observed in IM mice 24 h post-surgery, a phenomenon associated with a decreased splenic expression level of the homeostatic chemokine CCL19. Splenic denervation restored the expression of CCL19 and partially prevented the reduction of splenocytes in IM mice. Treatment with CYM-5442 prevented the egress of splenocytes but did not ameliorate the intestinal inflammation underlying postoperative ileus.
Intestinal manipulation results in two distinct phenomena: local intestinal inflammation and a decrease in splenic cellularity. The splenic response relies on an alteration of cell trafficking in the spleen and is partially regulated by the splenic nerve. The spleen however does not participate in the intestinal inflammation during POI.
术后肠梗阻的特征是腹部手术后胃肠道蠕动出现短暂受损。肠道处理引发的肠道炎症是胃肠道运动功能长期失调的主要原因。肠道的二级淋巴器官被认为是炎症扩散至整个胃肠道（即所谓的场效应）的关键组成部分。然而，脾脏在其中的作用仍不明确。
在本研究中，我们探究脾脏是否会对肠道处理产生反应，并参与术后肠梗阻潜在的肠道炎症过程。
对小鼠进行剖腹术（L）或剖腹术加肠道处理（IM）。24小时后，通过定量聚合酶链反应（QPCR）评估肠道和结肠炎症，并测量肠道转运情况。通过QPCR分析脾脏中稳态趋化因子，并用流式细胞术分析脾细胞群体。在L/IM术后10小时给予鞘氨醇-1-磷酸受体1（S1P1）激动剂CYM-5442，以阻断细胞从脾脏流出。
术后24小时，IM组小鼠脾脏重量和细胞数量显著下降，这一现象与脾脏中稳态趋化因子CCL19的表达水平降低有关。脾脏去神经支配恢复了CCL19的表达，并部分阻止了IM组小鼠脾细胞数量的减少。CYM-5442处理可阻止脾细胞流出，但并未改善术后肠梗阻潜在的肠道炎症。
肠道处理会导致两种不同现象：局部肠道炎症和脾细胞数量减少。脾脏的反应依赖于脾脏中细胞转运的改变，并部分受脾神经调节。然而，在术后肠梗阻期间，脾脏并不参与肠道炎症。
