The protective effect of caveolin-1 on lung injury in rats ventilated through p38 MAPK signaling pathway

doi:10.3969/j.issn.1002-1949.2014.12.020

Abstract：Objective To investigate the expression of caveolin -1(Cav -1) under different ventilator conditions and to explain clearly the relationship between the expressions of Cav -1 and the activation of p38 MAPK signal in lung tissue in stress injury model .Methods Fifty-six healthy male SD rats (weighting 220~330 g) were randomly assigned into 7 groups according to the tidal volume (VT), respiratory rate (RR) and duration of mechanical ventilation.They were spontaneous breathing control group (group A) which was only done tracheotomy;protective mechanical ventilation group (group B1 and B2) with VT of 6 mL/kg and RR of 60 bpm, and B1 and B2 group ventilation duration was 1 h and 2 h, respectively;Large-tidal volume ventilation group ( group C1, C2, D1, D2, VT 30 mL/kg, RR 40 bpm, ventilation duration 1 h, 2 h), but only rat in group D1 and D2 were intraperitoneally injected with SB203580, a specific inhibitor of p38 MAPK.Hemodynamic parameters and arterial blood gases of all the rats in the 7 groups were measured throughout the study period .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. Lung pathological changes were observed by microscopy .The protein levels of Cav -1, p38 MAPK, and AP-1 in lung tissues were assayed with immunohistochemistry staining .The expression levels of Cav-1, MKK3, p38 MAPK mRNA in lung tissue were measured by reverse transcription -polymerase chain reaction (RT-PCR).Lung myeloperoxidase (MPO) activity and wet-dry weight ratio (W/D) were measured.The levels of total protein and interleukin-6 (IL-6) in BALF were measured by enzyme-link immunosorbent assay (ELISA).Results Compared with normal control group A, the expression of p38 MAPK, MKK3, Cav-1 mRNA and Cav -1, p38 MAPK protein was significantly up -regulated; the W/D ratio, MPO, concentration of IL -6 in BALF and total protein increased in group C; however, AP -1 protein was significantly down-regulated.The expression of p38 MAPK, MKK3, Cav-1 mRNA and Cav -1, p38 MAPK protein were significantly higher in group C than those in group of B; the W/D ratio, MPO, concentration of IL-6 in BALF and total protein were increased, but AP-1 protein was significantly lower in group C compared with group B.Compared with group C, expression of p38 MAPK, MKK3 mRNA and p38 MAPK protein was significantly lower in group D while Cav-1 mRNA, Cav-1 and AP-1 protein.W/D ratio, MPO, concentration of IL-6 in BALF and total protein were increased.Conclusion Cav-1 and the activation of p38 MAPK signal in lung tissue participate in the protective effects of the ventilator -induced lung injury.