Xuebijing Injection Ameliorates H 2 S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression

Objective To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H 2 S)-induced acute respiratory distress syndrome (ARDS). Methods Sprague-Dawley rats were exposed to H 2 S (300 ppm) to establish ARDS model, while human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a H 2 S donor, 500 µmol/L) to establish cell model. H 2 S and XBJ were concurrently administered to the rat and cell models. Lung hematoxylin and eosin staining, immunohistochemistry, transmission electron microscopy and wet/dry ratio measurement were used to confirm ARDS induced by H 2 S in vivo . The expression levels of claudin-5, phosphorylated protein kinase B (p-AKT)/t-AKT and p-forkhead box transcription factor O1 (FoxO1)/t-FoxO1 in vivo and in vitro were also assessed. Paracellular permeability and transepithelial electrical resistance (TEER) were measured to evaluate endothelial barrier function in the cell model. Results The morphological investigation showed that XBJ attenuated H 2 S-induced ARDS in rats. XBJ significantly ameliorated both the reduction in TEER and the increased paracellular permeability observed in NaHS-treated HPMECs ( P <0.05). The protective effects of XBJ were blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K)/AKT/FoxO1 pathway antagonist ( P <0.05). Furthermore, XBJ promoted the expression of claudin-5 and increased the levels of p-AKT and p-FoxO1 in vivo and in vitro ( P <0.05). Conclusions XBJ ameliorated H 2 S-induced ARDS by promoting claudin-5 expression via the PI3K/AKT/FoxO1 signaling pathway.