ObjectiveTo explore the effects of inhibition of paxillin phosphorylation on ventilation associated lung injury. MethodsSixty healthy male SD rats were randomly divided into four groups, namely a control group, a protective ventilation group, a high tidal volume ventilation group, and an inhibitor group. The rats in the control group received only tracheotomy and breathe naturally. The rats in the protective ventilation group received protective ventilation for 2 hours. The rats in the high tidal volume ventilation group and the inhibitor group received high tidal volume ventilation for 2 hours. The rats in the inhibitor group additionally received intraperitoneal injection of tyrosine protein kinase inhibitor PP2 before ventilation. All rats were sacrificed and the specimens of lung tissue were collected. The pathological changes of lungs were observed under light microscope and estimated by the diffuse alveolar damage (DAD) score system. The activity of myeloperoxidase (MPO) and the lungs wet/dry (W/D) weight ratio were measured. The expression of tumor necrosis factor-α(TNF-α) in BALF was detected by ELISA. Evans blue (EB) method was used to detect the pulmonary vascular permeability. The expression levels of phosphorylated paxillin (p-paxillin) and paxillin in lung tissue were measured by Western blot. Apoptosis in situ was detected by TUNEL. ResultsThere were significant differences in the W/D ratio, the EB extravasation, DAD score, the MPO activity and the TNF-αexpression in BALF between the high tidal volume ventilation group and the inhibitor group (P < 0.05). The apoptosis rate of each group was sorted from high to low as the high tidal volume ventilation group, the inhibitor group, the protective ventilation group, and the control group. The expression level of p-paxillin was the highest in the high tidal volume ventilation group which was significantly different from other groups (all P < 0.05). There was no significant difference in the expression of paxillin in the protective ventilation group, the high tidal volume ventilation group and the inhibitor group (P > 0.05). ConclusionInhibition of paxillin phosphorylation can significantly alleviate mechanical ventilation associated lung injury.