Rosuvastatin enhances alveolar fluid clearance in lipopolysaccharide-induced acute lung injury by activating the expression of sodium channel and Na,K-ATPase via the Pi3K/AKT/Nedd4-2 pathway

Abstract

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating clinical conditions characterized by pulmonary epithelial damage and protein-rich fluid accumulation in the alveolar spaces. Statins are a class of HMG-CoA reductase inhibitors, which exert cholesterol-lowering and anti-inflammatory effects. Methods: Rosuvastatin (1 mg/kg) was injected intravenously in rats 12 h before lipopoly-saccharide (LPS, 10 mg/kg) administration. Eight hours later after LPS challenge, alveolar fluid clearance (AFC) was detected in rats (n = 6–8). Rosuvastatin (0.3 µmol/mL) and LPS were cultured with primary rat alveolar type II epithelial cells for 8 h. Results: Rosuvastatin obviously improved AFC and attenuated lung-tissue damage in ALI model. Moreover, it enhanced AFC by increasing sodium channel and Na,K-ATPase protein expression. It also up-regulated P-Akt via reducing Nedd4-2 in vivo and in vitro. Furthermore, LY294002 blocked the increase in AFC in response to rosuvastatin. Rosuvastatin-induced AFC was found to be partly rely on sodium channel and Na, K-ATPase expression via the PI3K/AKT/Nedd4-2 pathway. Conclusion: In summary, the findings of our study revealed the potential role of rosuvas-tatin in the management of ALI/ARDS.