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

Background: Evidence 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. Methods: In 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). Results: The 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. 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. (c) 2021 Elsevier Ltd and ISBI. All rights reserved.

Automated summary

The study showed that dexmedetomidine treatment mitigated burn-induced intestinal barrier injury by inhibiting the MLCK/p-MLC signaling pathways, reducing histological damage, enhancing tight junction protein expression, and decreasing inflammation levels.