P38 mitogen-activated protein kinase inhibition attenuates mechanical stress induced lung injury via up-regulating AQP5 expression in rats

Abstract

The aim of this study was to detect aquaporin-5 (AQP5) expression and evaluate the role of the p38-MAPK signalling pathway in mechanical ventilation-associated lung injury. Rats were randomly divided into 5 groups. In Group C, only trachea were cut to retain spontaneous breathing; in Group S and Group L, rats were ventilated with tidal volumes at 12 or 40 mL/kg for 4 h; in Group S + I and Group L + I, rats were given the p38-MAPK inhibitor SB203580 before ventilation. The protein expressions were measured using immunochemistry and western blot. The wet/dry weight ratio (W/D) of the lung tissue was calculated. Broncho-alveolar lavage fluid was collected to examine the pulmonary neutrophil (PMN) count and inflammatory cytokines. Compared with Group C, the other four groups had decreased AQP5 level, along with the increased p38 MAPK level, p-p38 MAPK level, W/D ratio, PMN count, levels of TNF-α and IL-6 and lung injury score (p < 0.05). Moreover, in Group L and Group L + I, the changes in these indicators were more significant than in Group S and Group S + I (p < 0.05), respectively, indicating that larger tidal volume induces more severe lung injury. However, after treatment with SB203580, the changes in the indicators in Group S + I and Group L + I were significantly attenuated compared to those in Group S and Group L, respectively (p < 0.05), suggesting that SB203580 could alleviate the lung injury induced by mechanical ventilation. The inhibition of the p38-MAPK pathway may decrease the occurrence of pulmonary edema induced by mechanical ventilation possibly by up-regulating AQP5 expression.

Keywords

• lung injury
• aquaporin-5
• p38 mapk
• mechanical ventilation