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

Chao Qin,Yi Jiang,Xing Chen,Yingxue Bian,Yaoqi Wang,Keliang Xie,Yonghao Yu

doi:10.1016/j.burns.2021.01.017

Abstract

BackgroundEvidence suggests that sedative dexmedetomidine can prevent intestinal dysfunction. However, the specific mechanisms of its protective effects against burn-induced intestinal barrier injury remain unclear. We aimed to explore the possible positive effects of dexmedetomidine on burn-induced intestinal barrier injury and the effects the myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) signalling pathway in an experimental model of burn injury. MethodsIn this study, the plasma concentration of fluorescein isothiocyanate-labelled dextran (FITC-dextran) was measured. 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 detected by enzyme-linked immunosorbent assay (ELISA). ResultsThe results shows 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. ConclusionsIn 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.

Highlights

Dexmedetomidine, a potent α2-adrenoceptor agonist with analgesic, sedative, antiinflammatory, and anti-apoptotic effects, is commonly used in patients with critical illness in intensive care units
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 myosin light chain kinase (MLCK) protein expression and myosin light chain (MLC) phosphorylation
In conclusion, dexmedetomidine exerted an anti‐inflammatory effect and protected tight junction complexes against burn‐induced intestinal barrier damage by inhibiting the MLCK/phosphorylated myosin light chain (p-MLC) signalling pathways, suggesting that it may be an effective drug in the treatment of burn-induced intestinal injury

Summary

Introduction

Dexmedetomidine, a potent α2-adrenoceptor agonist with analgesic, sedative, antiinflammatory, 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. The specific mechanisms of its protective effects against burn-induced intestinal barrier injury remain unclear. 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

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