Protection of the ventilation-induced lung injury by inhibiting Caveolin-1 phosphorylation

doi:10.3969/j.issn.1002-1949.2015.08.015

Abstract：Objective To define the protective role of Caveolin-1 phosphorylation in the lung injury induced by ventilation.Methods Fifty healthy male SD rats were randomly divided into five groups:A, B1, B2, C1, C2 groups (n=10).Group A served as control group, in which rats did not receive ventilation.Groups B1, B2, C1 and C2 received large-tide volume ventilation, but only rats in groups C1 and C2 received tyrosine kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2, 5 mg/kg respective) 1 hour before ventilation.After maintaining ventilation for 1 h or 2 h, all rats were sacrificed and specimens of lung tissues and bronchoalveolar lavage fluid ( BALF) were harvested.Mean arterial pressure ( MAP) was observed continuously.Lung pathological changes were observed by microscopy and diffuse alveolar damage ( DAD ) score were estimated.The protein levels of eNOS and interleukin-1 receptor-associated kinase 4 ( IRAK4 ) in lung tissues were determined by immunohistochemistry staining.The expression levels of P -Cav -1 ( Y14) and Cav-1 in lung tissue were measured by Western Blotting.Lung myeloperoxidase ( MPO) activity was measured by colorimetric analysis, wet-dry weight ratio ( W/D) was measured.The levels of tumor necrosis factor -α( TNF -α) in BALF were measured by enzyme -linked immunosorbent assay ( ELISA ) .Evans Blue was used to detect the pulmonary vascular permeability.Arterial blood gases were measured every one hour. Results Comparison with group A, there was statistical significance in the expression of Cav-1, eNOS and IRAK4, protein in lung tissue, W/D ratio, the amount of Evans blue extravasation, diffuse alveolar damage ( DAD) score, MAP, arterial blood gas analyses, as well as the amount of MPO and TNF-αin BALF among group A, group B1, group B2, group C1 and group C2 (all P<0.05).Comparison with group A there was statistical significance in the expression of P -Cav -1 among the five groups but group C2 (P >0.05).There were statistical significances in the all detection index (all P<0.05) but the expression of Cav-1 (P>0.05) between C1 and group B1, and similar results were shown when compared C2 and B2 groups.Conclusion Inhibition of phosphorylation of caveolin -1 can reduce pulmonary capillary permeability and inhibit inflammatory factors and inflammatory cell migration thus to play a protective role on ventilator-induced lung injury in rats.