Hydrogen-rich saline prevents the down regulation of claudin-5 protein in septic rat lung via the PI3K/Akt signaling pathway

Background: Acute lung injury (ALI) is characterized by capillary leak and increased pulmonary permeability with high mortality. Hydrogen-rich saline, which has therapeutic anti-inflammatory and anti-apoptotic activity, can attenuate pulmonary edema in sepsis-related lung injury. However, the mechanisms of the protective effect are not completely clear. Thus, we investigated the effects and mechanisms of hydrogen-rich saline on the expression of claudin-5 protein which is associated with endothelial paracellular permeability in lipopolysaccharide (LPS)-induced ALI. Methods: Sixty male Sprague-Dawley rats, which were randomly divided into six groups (n = 10, in each group): control group, LPS group, LPS+H2 group, H2 group, LPS+H2+LY294002 group and LPS+LY294002 group, received intratracheal administration of LPS followed by intraperitoneal injection of hydrogen-rich saline or intravenous injection of PI3K inhibitor LY294002. The severity of pulmonary edema was assessed by wet-to-dry rate and Evans blue infiltration; the expression of claudin-5 protein was examined by immunofluorescence double-labeling staining and western blot; the level of phospho-Akt was detected by immunohistochemistry staining and western blot. Results: Pretreatment with hydrogen-rich saline significantly alleviated pulmonary edema and attenuated the deterioration of claudin-5 protein induced by LPS in rat lung. Moreover, Hydrogen-rich saline enhanced LPS-induced activation of the PI3K/Akt pathway, which is associated with the regulation of claudin-5 expression. However, the protective effects of hydrogen-rich saline were partly suppressed by LY294002. Conclusion: Hydrogen-rich saline ameliorates LPS-induced ALI through reducing disruption of claudin-5 protein, which may be associated with the enhanced activation of the PI3K/Akt pathway.