[Xuebijing Injection ameliorates sepsis-associated acute respiratory distress syndrome in mice by upregulating phospholipid transfer protein to regulate macrophage JNK/c-JUN pathway].

OBJECTIVES: To investigate the ameliorative effect of Xuebijing Injection in a mouse model of sepsis-associated acute respiratory distress syndrome (ARDS) and its molecular mechanisms.

METHODS: In a C57BL/6J mouse model of sepsis-associated ARDS induced by lipopolysaccharide (LPS), the ameliorative effect of pretreatment with Xuebijing injection at low and high doses prior to modeling were evaluated by analyzing survival rates, lung histopathology, levels of inflammatory cytokines, and expressions of phospholipid transfer protein (PLTP) using transcriptomics, qPCR, Western blotting, ELISA, and immunofluorescence staining. In the cell experiment, RAW264.7 macrophages treated with LPS and different concentrations of Xuebijing were examined for changes in cell viability, morphology, inflammatory cytokine levels, and PLTP expression. PLTP overexpression experiment was carried out to verify the function of PLTP, and the changes in expressions of JNK/c-JUN and NF-κB pathway proteins were detected.

RESULTS: Xuebijing pretreatment, especially at the high dose, significantly increased the 4-day survival rate, reduced lung histopathological injury score, and decreased lung wet/dry weight ratio in mice with sepsis-associated ARDS. High-dose Xuebijing more effectively lowered serum levels of TNF-α, IL-6, and IL-1β than the low dose, while at both doses, Xuebijing significantly decreased IL-1β levels in the bronchoalveolar lavage fluid (BALF); Xuebijing at the high dose, but not the low dose, significantly reduced BALF levels of TNF‑α and IL-6. LPS significantly downregulated PLTP expression in mouse lung tissue, a trend effectively ameliorated by Xuebijing pretreatment. In cultured RAW264.7 cells, Xuebijing dose-dependently inhibited LPS-induced inflammatory cytokine release and upregulated PLTP expression, resulting also in suppressed phosphorylation and activation of the JNK/c-JUN and NF-κB signaling pathways, and this effect was significantly enhanced by PLTP overexpression.

CONCLUSIONS: Xuebijing alleviates sepsis-associated ARDS by upregulating PLTP and inhibiting JNK/c-JUN and NF-κB signaling pathways, suggesting the potential of PLTP as a therapeutic target for this condition.