Objective To explore the mechanism of Qingwen Baidu Drink in treating sepsis-induced lung injury.

Methods One hundred C57BL/6 mice were randomly divided into blank group, model group, Qingwen Baidu Drink low-dose group, Qingwen Baidu Drink medium-dose group, and Qingwen Baidu Drink high-dose group, with 20 mice in each group. HE staining was used to examine the pathological changes of lung tissues. ELISA was used to detect the expression levels of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), chemokine ligand 10 (CXCL10) and plasma coagulation factor Ⅲ (F3). qPCR was used to detect the mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2 (COX-2) and interferon-γ (IFN-γ) in lung tissues. The number of platelets (PLT) in plasma was analyzed by routine blood analysis instrument. Immunofluorescence analysis was used to detect vascular endothelial cadherin (VE-cadherin), endothelial adhesion junction marker occludin 5 (CLDN5) and pericyte marker neuronal collagen antigen 2 (NG2) in alveolar capillary endothelial cells. Western blot was used to detect the protein expression levels of cysteine-containing aspartate proteinase 11 (Caspase11), GSDMD and GSDMD-N in mouse lung tissues.

RESULTS Compared with the blank group, the lung tissue of the mice in the model group showed obvious pathological damage. The levels of serum IL-1β, TNF-α, and CXCL10 and the mRNA expression levels of MCP-1, COX-2, and IFN-γ in lung tissue were significantly increased (P < 0.01), and the number of PLT and the content of F3 in plasma were significantly decreased (P < 0.01). The fluorescence expression of VE-cadherin, CLDN5, and NG2 proteins in lung tissue was significantly enhanced(P < 0.01), while the expression of Caspase11 and GSDMD-N proteins was increased (P < 0.01). Compared with the model group, the pathological damage of the lung tissue of the mice in all doses of Qingwen Baidu Drink groups was alleviated, the levels of serum IL-1β, TNF-α, and CXCL10 and the mRNA expression levels of MCP-1, COX-2, and IFN-γ in lung tissue were significantly decreased (P < 0.05, P < 0.01), and the number of PLT and the content of F3 in plasma were increased (P < 0.05, P < 0.01); the fluorescence expression of VE-cadherin, CLDN5, and NG2 proteins in lung tissues was weakened (P < 0.05, P < 0.01), and the expression of Caspase11 and GSDMD-N/GSDMD proteins was reduced (P < 0.05, P < 0.01).

CONCLUSION Qingwen Baidu Drink can inhibit the activation of GSDMD-N and Caspase11, reduce the release of inflammatory factors, decrease blood loss and damage to vascular barrier function, and thus improve the lung injury caused by sepsis.