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Dexmedetomidine protects against burn-induced intestinal barrier injury via the MLCK/p-MLC signalling pathway

Authors :
Keliang Xie
Yaoqi Wang
Yingxue Bian
Yi Jiang
Yonghao Yu
Chao Qin
Xing Chen
Source :
Burns : journal of the International Society for Burn Injuries. 47(7)
Publication Year :
2020

Abstract

Background Dexmedetomidine, a potent α2-adrenoceptor agonist with analgesic, sedative, anti-inflammatory, and anti-apoptotic effects, is commonly used in patients with critical illness in intensive care units. Accumulating evidence indicates that dexmedetomidine can protect against intestinal dysfunction. However, the specific mechanisms of its protective effects against burn-induced intestinal barrier injury remain unclear. Here, we aimed to explore the possible positive effects of dexmedetomidine on burn-induced intestinal barrier injury and the role of the myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) signalling pathway in an experimental model of burn injury.Methods In this study, the intestinal permeability of burn-induced intestinal barrier damage was assessed by estimating the plasma concentration of 4.4 kDa fluorescein isothiocyanate-labelled dextran (FITC-dextran). Histological changes were evaluated using haematoxylin and eosin (HE) staining. Tight junction proteins were evaluated by western blot and immunofluorescence analyses to assess the structural integrity of intestinal tight junctions. The level of inflammation was determined by enzyme-linked immunosorbent assay (ELISA).Results Our findings demonstrated that the increase in intestinal permeability caused by burn injury is accompanied by histological damage to the intestine, decreases in the expression of the tight junction proteins Zonula Occludens-1 (ZO-1) and Occludin, increases in inflammatory cytokine levels and elevation of both MLCK protein expression and MLC phosphorylation. After dexmedetomidine treatment, the burn-induced changes were ameliorated.Conclusions In conclusion, dexmedetomidine exerted an anti‑inflammatory effect and protected tight junction complexes against burn‑induced intestinal barrier damage by inhibiting the MLCK/p-MLC signalling pathways, suggesting that it may be an effective drug in the treatment of burn-induced intestinal injury.Trial registration Not appliance.

Details

ISSN :
18791409
Volume :
47
Issue :
7
Database :
OpenAIRE
Journal :
Burns : journal of the International Society for Burn Injuries
Accession number :
edsair.doi.dedup.....3db15b17f4765f755d48d91d585c604c