Dexmedetomidine enhances anastomotic healing partly via the Wnt/β-catenin pathway in a rat model of colon surgery

Abstract

BACKGROUND

Colorectal surgery is often associated with a high risk of anastomotic leakage. Intraoperative administration of dexmedetomidine (DEX) can improve postoperative gastrointestinal function.

AIM

To investigate the effects of DEX on anastomotic healing in a rat model of intestinal anastomosis (IA).

METHODS

Rats were randomly divided into three groups: Sham (underwent abdominal only opening and closure), IA, and IA + DEX. In the IA + DEX group, DEX (5 μg/kg) was administered via tail vein infusion one day before and after anesthesia. Intestinal function, inflammation, and barrier integrity were measured based on intestinal propulsion, anastomotic burst pressure, histopathological analysis, immunohistochemical staining, enzyme-linked immunosorbent assay, and Western blotting. In vitro, IEC-6 cells faced lipopolysaccharide-induced injury. DEX (4.8 μmol/L) effects on viability, apoptosis, and tight junction proteins were tested with/without the Wnt pathway inhibitor dickkopf-1 (DKK-1) (20 ng/mL). β-catenin, glycogen synthase kinase-3 beta (GSK-3β), claudin-1, and zonula occludens-1 (ZO-1) were assessed by Western blot.

RESULTS

Compared with IA, IA + DEX showed a non-significant increase in intestinal propulsion on postoperative day 6 and a significant rise in anastomotic burst pressure on day 7. Histology indicated reduced inflammation and submucosal injury. Serum tumor necrosis factor-alpha and diamine oxidase decreased, while tight junction proteins (claudin-1, ZO-1) increased in IA + DEX. High-throughput sequencing and Western blotting suggested activation of the Wnt/β-catenin pathway as a potential mechanism. In vitro, DEX pretreatment attenuated lipopolysaccharide-induced downregulation of claudin-1 and ZO-1 and reduced apoptosis in IEC-6 cells. These protective effects were reversed by DKK-1, which abolished DEX-mediated Wnt/β-catenin activation (decreased β-catenin, increased GSK-3β) and nullified the benefits of DEX on tight junction protein expression.

CONCLUSION

DEX enhances anastomotic healing and barrier function after IA, partly via Wnt/β-catenin activation, indicating therapeutic potential to improve postoperative outcomes.

Keywords: Intestinal anastomosis; Dexmedetomidine; Tight junction proteins; Wnt/β-catenin; Signaling pathway

Core Tip: Dexmedetomidine (DEX), a selective α2-adrenergic agonist, significantly enhances anastomotic healing in rat models of colon surgery. Our study demonstrates that perioperative DEX administration improves intestinal barrier integrity by upregulating tight junction proteins (claudin-1/zonula occludens-1), reduces systemic inflammation (suppressed tumor necrosis factor-alpha/diamine oxidase/intestinal fatty acid-binding protein), and increases anastomotic burst pressure. Crucially, we identify activation of the Wnt/β-catenin pathway as a novel mechanistic driver for DEX-mediated repair. These findings reveal DEX’s dual role in barrier protection and regeneration, supporting its potential as a perioperative adjuvant to mitigate anastomotic leakage risk in abdominal surgery.