PD98059, SB203580, and Akt-deficient mice reduced stretch-induced microvascular leak, lung fibrosis, and chemokine production. After 5 days of bleomycin administration, wild-type C57BL/6 (WT) mice or serine/threonine kinase-protein kinase B (Akt)+/- mice ventilated at a tidal volume (VT) of 6 ml/kg or 30 ml/kg for 5 hours were pretreated with 2 mg/kg PD98059 or 16 mg/kg SB203580 subcutaneously for 30 minutes. (a) Evans blue dye (EBD) assay and (b) the hydroxyproline (OH) content were obtained from lung tissues of mice (n = 6 per group). (c) Macrophage inflammatory protein-2 (MIP-2) production and (d) 10 kDa IFNγ-inducible protein (IP-10) production were obtained from bronchoalveolar lavage (BAL) fluid of mice (n = 6 per group). *P < 0.05 versus control, nonventilated mice with bleomycin pretreatment; †P < 0.05 versus all other groups; ‡P < 0.05 versus control, nonventilated mice without bleomycin pretreatment.
Li et al. Critical Care 2008 12:R103 doi:10.1186/cc6983