Potentiation of serotonin signaling protects against intestinal ischemia and reperfusion injury in mice.

Autor: Tackett JJ; Department of Surgery, Yale University School of Medicine, New Haven, Connecticut., Gandotra N; Department of Surgery, Yale University School of Medicine, New Haven, Connecticut., Bamdad MC; Department of Surgery, Yale University School of Medicine, New Haven, Connecticut., Muise ED; Department of Surgery, Yale University School of Medicine, New Haven, Connecticut., Cowles RA; Department of Surgery, Yale University School of Medicine, New Haven, Connecticut.
Jazyk: angličtina
Zdroj: Neurogastroenterology and motility [Neurogastroenterol Motil] 2019 Mar; Vol. 31 (3), pp. e13498. Date of Electronic Publication: 2018 Nov 04.
DOI: 10.1111/nmo.13498
Abstrakt: Background: Knock-out of serotonin re-uptake transporters (SERT) or use of selective serotonin re-uptake inhibitors (SSRIs) potentiates enteric serotonin (5-HT) signaling and stimulates enterocyte proliferation. We hypothesized that increased serotonin signaling would mitigate epithelial injury from intestinal ischemia and reperfusion (I/R).
Methods: Mice lacking SERT (SERTKO mice) and wild-type littermates (WTLM) were subjected to intestinal ischemia by superior mesenteric artery (SMA) occlusion. At intervals post-laparotomy with or without ischemia, ileum was harvested and prepared for staining. A WTLM subgroup treated with SSRI after SMA occlusion followed by reperfusion was also sacrificed and analyzed. Mucosal injury was scored, percentage of injured villi calculated, and enterocyte proliferation measured. Lastly, staining for enterocytes, enteroendocrine cells, and goblet cells, villus epithelial cellular make-up was investigated at baseline and 14 days after injury. Measurements were compared between groups using t test and chi-squared test.
Key Results: Mucosal injury after I/R was significantly decreased in SERTKO and SSRI-treated mice compared to WTLM at all intervals except baseline. Enterocyte proliferation was greater in SERTKO and SSRI-treated mice without alteration in cellular composition along villi (P > 0.05).
Conclusions and Inferences: Potentiation of 5-HT signaling is associated with mucosal protection from intestinal I/R injury without alterations in villus cell distribution, possibly via increased rates of enterocyte renewal.
(© 2018 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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