Xuebijing Injection Ameliorates HS-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 (HS)-induced acute respiratory distress syndrome (ARDS).

Methods: Sprague-Dawley rats were exposed to HS (300 ppm) to establish ARDS model, while human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a HS donor, 500 µmol/L) to establish cell model. HS 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 HS 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 HS-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 HS-induced ARDS by promoting claudin-5 expression via the PI3K/AKT/FoxO1 signaling pathway.