南京中医药大学学报2025,Vol.41Issue(11):1480-1492,13.DOI:10.14148/j.issn.1672-0482.2025.1480
基于脂质组学探究散寒化湿方治疗呼吸道合胞病毒肺炎模型小鼠的作用机制
Lipidomics-Based Study on the Mechanism of Sanhan Huashi Formula in Treating Respiratory Syncytial Virus Pneumonia Model Mice
摘要
Abstract
OBJECTIVE To investigate the therapeutic effect of Sanhan Huashi Formula(SHF)on respiratory syncytial virus(RSV)-infected mouse models and explore its potential antiviral and anti-inflammatory mechanisms using lipidomics.METHODS Fifty-four BALB/c mice were randomly divided into six groups(n=9):blank group,model group,Ribavirin group(50 mg·kg-1·d-1),and SHF high(15.46 g·kg-1·d-1),medium(7.73 g·kg-1·d-1),and low-dose(3.87 g·kg-1·d-1)groups.A pneumonia model was established by in-tranasal RSV infection,followed by three consecutive days of oral gavage administration.Lung tissues were collected for histopathologi-cal evaluation using hematoxylin-eosin(HE)staining and inflammation scoring.Real-time quantitative polymerase chain reaction(RT-qPCR)was performed to measure mRNA levels of viral gene fusion protein(F),glycoprotein(G),and inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)to assess lung viral load and inflammation,while immunofluorescence staining was performed to observe the expression of RSV-F protein in lung tissues.Serum lipidomics analysis was conducted using ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q Exactive Or-bitrap MS)to identify lipid metabolism changes and differential lipids.RESULTS Compared with the blank group,mice in the model group exhibited marked pulmonary inflammatory cell infiltration and tissue injury,with significantly elevated pulmonary histopa-thology scores and lung index.The lung viral load and the mRNA expression levels of the inflammatory factors TNF-α and IL-6 were significantly increased,and immunofluorescence likewise indicated high expression of RSV-F protein in lung tissue.Relative to the model group,treatment with SHF at all tested doses clearly ameliorated lung tissue injury,effectively suppressed viral gene expression and inflammatory cytokine levels,and reduced the fluorescence signal intensity of RSV-F protein in the lungs.Lipidomics analysis re-vealed that compared with the blank group,the model group exhibited marked disturbances in lipid metabolism-characterized by dys-regulation of triacylglycerol(TG),phosphatidylcholine(PC),lysophosphatidylcholine(LPC),sphingomyelin(SM),diacylglycerol(DG),lysophosphatidylethanolamine(LPE),and phosphatidylethanolamine(PE).High-dose SHF treatment reversed these RSV-induced lipid abnormalities.CONCLUSION SHF effectively alleviates RSV-induced pulmonary inflammation and pathological injury,re-duces pulmonary RSV viral load,and may exert these effects by modulating dysregulated lipid metabolism in peripheral blood.关键词
散寒化湿方/呼吸道合胞病毒/肺炎/脂质组学/超高效液相色谱-四极杆-静电场轨道阱高分辨质谱法/宿主免疫/脂质Key words
Sanhan Huashi Formula/respiratory syncytial virus/pneumonia/lipidomics/ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry/host immunity/lipids分类
医药卫生引用本文复制引用
朱钰晴,陶柯宇,熊应财,张计茹,张钊玮,周小晴,谭佳妮,纪建建..基于脂质组学探究散寒化湿方治疗呼吸道合胞病毒肺炎模型小鼠的作用机制[J].南京中医药大学学报,2025,41(11):1480-1492,13.基金项目
国家重点研发计划(2023YFC2308200) (2023YFC2308200)
江苏省高等学校基础科学(自然科学)研究重大项目(22KJA360004) (自然科学)
2025年度江苏省中医流派研究院重点课题(LPZD2025012) (LPZD2025012)