The Effect Of Low Tidal Volume Ventilation Preconditioningon Lipopolysaccharide-induced Acute Lung Injury In Rats

Objective Effects of low tidal volume (LTV) ventilation preconditioning in endotoxin-induced acute lung injury (ALI) have not been studied. We investigated the effect of LTV ventilation pretreatment on ALI induced by lipopolysaccharide (LPS) in rats.Methods Forty-eight healthy male SD rats, weighing 250-300g,8-12 weeks, were randomly divided into 4 groups(n=12 each):(i) sham rats injected (i.p.) with 0.5m10.9% (physiologic) saline; sham rats pretreated with tidal volume 6 mL/kg ventilation for 1 h followed by injection (i.p.) of 0.5mlphysiologic saline (MV-saline group); (ⅲ) rats injected with LPS (i.p.) 40 mg/kg dissolved in 0.5 ml saline (LPS group); rats pretreated with tidal volume 6 mL/kg ventilation for 1 h before injection (i.p.) with LPS (MV-LPS group). Animals were observed for 6 h and sacrificed.Tumor necrosis factor(TNF)-a, interleukin(IL)-1β and IL-6 concentrations in bronchoalveolar lavage fluid(BALF)were determined(by ELISA). Lungs were removed formeasurement of lung wet-to-dry ratio (W/D ratio), Evans Blue Dye extravasation, microscopic examination and the lung injury was scored. Lung tissue cell apoptosis was also determined (by TUNEL) and the apoptosis index (AI) was calculated, the expression of pulmonary RhoA, ROCK2 mRNA(by RT-PCR), and ROCK1 protein (by Immunohistochemical staining and Western blot method) in lung alveolar cells were determined.Results Compared with sham group,the lung injury score, W/D ratio,AI,extravasation of Evans Blue Dyein alveolar and a variety of inflammatory cytokines, like TNF-a,IL-1β and IL-6were significantly increased in LPS group and MV-LPS group(P<0.05), and expression of pulmonary RhoA, ROCK2 mRNA, and ROCK1 protein were also up-regulated(P<0.05); compared withLPS group.the lung injury score, W/D ratio,AI,extravasation of Evans Blue Dye in alveolar and a variety of inflammatory cytokines, like TNF-a,IL-1β and IL-6 were significantlydecreased in MV-LPS group(P<0.05), and expression of pulmonary RhoA, ROCK2 mRNA, and ROCK1 protein were also reduced(P<0.05).Conclusion LPS could caused severe ALI,LTV ventilation preconditioning can attenuate release of pulmonary pro-inflammatory cytokines and decrease the AI induced by severe sepsis. Early protection seems to be mediated partly through inhibition of activation of a Rho pathway.