摘要
[目的]探讨鱼腥草素钠(SH)对脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠肠道菌群的影响及其可能作用机制。[方法]18只SPF级雄性BALB/c小鼠(6~8周龄,体质量18~22 g)随机分为对照组、模型组(LPS组)和SH组(LPS+SH),每组6只。对照组和LPS组灌胃生理盐水,SH组灌胃SH(100 mg/kg),每日1次,除对照组外,模型组和SH组连续给药7 d后气管内注射5 mg/kg LPS建立ALI模型。小鼠建模前后称质量,实验结束后测定肺湿质量/干质量(W/D)比,苏木精-伊红(HE)染色观察病理变化,酶联免疫吸附测定(ELISA)炎症因子水平,蛋白质免疫印迹测定JNK/p38信号通路蛋白水平,采用16S rRNA分析肠道菌群。[结果]SH能降低LPS诱导的ALI小鼠的W/D比值,改善肺组织病理损伤,抑制肺组织中髓过氧化物酶(MPO)活性、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)及白细胞介素-6(IL-6)的水平,抑制p-JNK和p-P38蛋白表达。SH显著改善ALI小鼠的肠道菌群α和β多样性,Firmicutes的相对丰度升高,而Proteobacteria的相对丰度降低,在属的水平上,模型组unidentified_Enterobacteriaceae、Bacteroides和Klebsiella的相对丰度增加,而Ligilactobacillus、Lactobacillus和Akkermansia的丰度降低,而在SH组观察到了相反的趋势。炎症指标及肺水肿与Proteobacteria、Klebsiella和g_unidentified_Enterobacteriaceae呈正相关,与Akkermansia、Lactobacillus和Ligilactobacillus呈负相关。[结论]SH在LPS诱导的ALI中具有保护作用,其潜在机制可能是通过抑制JNK/p38信号通路炎症反应,以及改善肠道菌群紊乱。
[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 theαandβdiversity 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_Enterobacteriaceae,Bacteroides and Klebsiella,and lower abundances of Ligilactobacillus,Lactobacillus and Akkermansia,whereas the opposite trend was observed in the SH group.Inflammatory markers and pulmonary edema positively correlated with Proteobacteria,Klebsiella and g_unidentified_Enterobacteriaceae,and negatively correlated with Akkermansia,Lactobacillus 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.
作者
郑春龙
段万石
ZHENG Chunong;DUAN Wanshi(Department of Thoracic Surgery,Second Affiliated Hospital of Air Force Military Medical University,Xi’an 710038,China)
出处
《天津中医药》
2025年第9期1177-1183,共7页
Tianjin Journal of Traditional Chinese Medicine
基金
陕西省重点研发计划项目(2024SF-YBXM-112)。
关键词
急性肺损伤
鱼腥草素钠
肠道菌群
炎症
acute lung injury
sodium houttuyfonate
gut microbiota
inflammation
