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Protective effects of sodium houttuyfonate on acute lung injury in mice and its impact on gut microbiota
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DOI   10.11656/j.issn.1672-1519.2025.09.13
Key Words   acute lung injury;sodium houttuyfonate;gut microbiota;inflammation
Author NameAffiliationE-mail
ZHENG Chunlong Department of Thoracic Surgery, Second Affiliated Hospital of Air Force Military Medical University, Xi'an 710038, China  
DUAN Wanshi Department of Thoracic Surgery, Second Affiliated Hospital of Air Force Military Medical University, Xi'an 710038, China drstoneduan@163.com 
Abstract
    [Objective] To investigate the effects of sodium houttuyfonate(SH) on gut microbiota in a mouse model of lipopolysaccharide(LPS)-induced acute lung injury(ALI) and explore its potential mechanisms of action. [Methods] Eighteen male SPF-grade BALB/c mice(6~8 weeks old,weighing 18~22 g) were randomly divided into three groups:control,model(LPS),and SH(LPS+SH),with six mice in each group. The control and LPS groups received oral gavage of normal saline,while the SH group received SH(100 mg/kg) once daily. Except for the control group,the model and SH groups were intratracheally injected with 5 mg/kg LPS after 7 days of continuous treatment to establish the ALI model. Mice were weighed before and after modeling. At the end of the experiment,lung wet-to-dry(W/D) ratios were measured,histopathological changes were observed using hematoxylin and eosin(HE) staining,inflammatory cytokine levels were assessed by enzyme-linked immunosorbent assay(ELISA),protein expression levels in the JNK/p38 signaling pathway were determined by Western blot,and gut microbiota composition was analyzed using 16S rRNA sequencing. [Results] SH reduced the W/D ratio,improved histopathological damage in lung tissue,and inhibited myeloperoxidase(MPO) activity,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6) levels in lung tissue. It also suppressed the expression of p-JNK and p-p38 proteins. SH significantly enhanced the α and β diversity of gut microbiota in ALI mice. The relative abundance of Firmicutes increased,while that of Proteobacteria decreased. At the genus level,the model group exhibited higher relative abundances of unidentified_EnterobacteriaceaeBacteroides and Klebsiella,and lower abundances of LigilactobacillusLactobacillus and Akkermansia,whereas the opposite trend was observed in the SH group. Inflammatory markers and pulmonary edema positively correlated with ProteobacteriaKlebsiellaand g_unidentified_Enterobacteriaceae,and negatively correlated with AkkermansiaLactobacillus and Ligilactobacillus. [Conclusion] SH exerts protective effects against LPS-induced ALI,potentially through inhibiting inflammatory responses mediated by the JNK/p38 signaling pathway and restoring gut microbiota balance.

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