Effects of baicalin on alveolar fluid clearance and α-ENaC expression in rats with LPS-induced acute lung injury

Baicalin has been reported to attenuate lung edema in the process of lung injury. However, the effect of baicalin on alveolar fluid clearance (AFC) and epithelial sodium channel (ENaC) expression has not been tested. Sprague-Dawley rats were anesthetized and intratracheally injected with either 1 mg/kg lipopolysaccharide (LPS) or saline vehicle. Baicalin with various concentrations (10, 50, and 100 mg/kg) was injected intraperitoneally 30 min before administration of LPS. Then lungs were isolated for measurement of AFC, cyclic adenosine monophosphate (cAMP) level, and cellular localization of alpha-ENaC. Moreover, mouse alveolar type II (ATII) epithelial cell line was incubated with baicalin (30 mu mol/L), adenylate cyclase inhibitor SQ22536 (10 mu mol/L), or cAMP-dependent protein kinase inhibitor (PKA) KT5720 (0.3 mu mol/L) 15 min before LPS (1 mu g/mL) incubation. Protein expression of alpha-ENaC was detected by Western blot. Baicalin increased cAMP concentration and AFC in a dose-dependent manner in rats with LPS-induced acute lung injury. The increase of AFC induced by baicalin was associated with an increase in the abundance of alpha-ENaC protein. SQ22536 and KT5720 prevented the increase of alpha-ENaC expression caused by baicalin in vitro. These findings suggest that baicalin prevents LPS-induced reduction of AFC by upregulating alpha-ENaC protein expression, which is activated by stimulating cAMP/PKA signaling pathway.