Ibuprofen Protects Ventilator-Induced Lung Injury by Downregulating Rho-Kinase Activity in Rats

Abstract EN

Background.

Ventilator-induced lung injury-(VILI-) induced endothelial permeability is regulated through the Rho-dependent signaling pathway.

Ibuprofen inhibits Rho activation in animal models of spinal-cord injury and Alzheimer’s disease.

The study aims to investigate ibuprofen effects on high tidal volume associated VILI.

Methods.

Twenty-eight adult male Sprague-Dawley rats were randomized to receive a ventilation strategy with three different interventions for 2 h: (1) a high-volume zero-positive end-expiratory pressure (PEEP) (HVZP) group; (2) an HVZP + ibuprofen 15 mg/kg group; and (3) an HVZP + ibuprofen 30 mg/kg group.

A fourth group without ventilation served as the control group.

Rho-kinase activity was determined by ratio of phosphorylated ezrin, radixin, and moesin (p-ERM), substrates of Rho-kinase, to total ERM.

VILI was characterized by increased pulmonary protein leak, wet-to-dry weight ratio, cytokines level, and Rho guanine nucleotide exchange factor (GEF-H1), RhoA activity, p-ERM/total ERM, and p-myosin light chain (MLC) protein expression.

Results.

Ibuprofen pretreatment significantly reduced the HVZP ventilation-induced increase in pulmonary protein leak, wet-to-dry weight ratio, bronchoalveolar lavage fluid interleukin-6 and RANTES levels, and lung GEF-H1, RhoA activity, p-ERM/total ERM, and p-MLC protein expression.

Conclusion.

Ibuprofen attenuated high tidal volume induced pulmonary endothelial hyperpermeability.

This protective effect was associated with a reduced Rho-kinase activity.