A study on circadian rhythm disorder of rat lung tissue caused by mechanical ventilation induced lung injury

Ventilator-induced lung injury (VILI), the most serious complication of mechanical ventilation therapy, is an excessive inflammatory response in lung tissue characterized by infiltration of inflammatory cells and overproduction of inflammatory mediators. The pathogenesis of VILI is very complex. It is becoming increasingly evident that disruption of circadian rhythm affects the immune response. Whether the pathogenesis of VILI is associated with circadian rhythm disruption has not been reported. In this study, we establish VILI model in SD rat by performing an endotracheal intubation and placing the rat on a mechanical ventilator (tidal volume of 40 ml/kg or 10 ml/kg without positive end-expiratory pressure). To examine the effect of VILI on clock gene expression, real-time quantitative PCR was performed to measure bmal1, clock, per2 and Rev-erb alpha mRNA expression. We found that Rev-erb alpha mRNA was significantly decreased in high tide volume mechanical ventilation group compared with spontaneous group, the same as REV-ERB alpha protein product which was tested by Western blot approach. Stimulation of REV-erb alpha activity by SR9009 greatly diminished VILI-induced lung edema, inflammatory cell infiltration and the production of the pro-inflammatory cytokine TNF-alpha. Collectively, our findings are the first to show that REV-ERB alpha plays an important role in VILI and inflammation, and circadian rhythm disorder in inflammation response may be a novel pathogenesis of VILI. (C) 2013 Elsevier B.V. All rights reserved.