Mechanism of Shenji Guben Prescription in Treating Chronic Obstructive Pulmonary Disease in Mice
10.13422/j.cnki.syfjx.20252225
- VernacularTitle:参吉固本方干预慢性阻塞性肺疾病小鼠模型的作用机制
- Author:
Zibo SUN
1
;
Jing YAO
1
;
Tingyu PAN
1
;
Qi ZHAO
1
;
Jing WANG
1
;
Jun ZHAO
1
;
Yong XU
2
;
Xianmei ZHOU
1
;
Yu WEI
1
;
Hailang HE
1
Author Information
1. Affiliated Hospital of Nanjing University of Chinese Medicine， Nanjing 210029， China
2. School of Chinese Medicine， Nanjing University of Chinese Medicine， Nanjing 210023， China
- Publication Type:Journal Article
- Keywords:
Shenji Guben prescription;
chronic obstructive pulmonary disease （COPD）;
transcriptomics;
lysosomal pathway;
therapeutic mechanism
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(22):159-168
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo evaluate the therapeutic effect of Shenji Guben prescription （SJGB） on chronic obstructive pulmonary disease （COPD） in mice and to explore its potential therapeutic mechanism via transcriptomics. MethodsA mouse model of COPD was established by combined exposure to lipopolysaccharide （LPS） and cigarette smoke. C57BL/6J mice were randomly allocated into a control group， a model group， an acetylcysteine （78 mg·kg-1·d-1） group， and low- （7.5 g·kg-1·d-1）， medium- （15 g·kg-1·d-1）， and high-dose （30 g·kg-1·d-1） SJGB groups. After 13 weeks of modeling， oral administration was initiated and continued for 28 days. The therapeutic effects of SJGB were assessed based on body weight， lung function， lung tissue pathology， and inflammatory factors in bronchoalveolar lavage fluid （BALF）. Ultra-high performance liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS） was employed to identify the active ingredients in SJGB. Transcriptomic profiling of lung tissue was performed by RNA-seq to identify differentially expressed genes （DEGs）， followed by gene ontology （GO） enrichment analysis， Kyotoencyclopedia of Genes and Genomes （KEGG） enrichment analysis， Gene Set Enrichment Analysis （GSEA）， and protein-protein interaction （PPI） network construction. Key genes were further validated by Western blot and Real‑time polymerase chain reaction （Real-time PCR）. ResultsAfter drug intervention， the final body weights of mice in medium- and high-dose SJGB groups were higher than those in the model group （P<0.05）. Compared with the model group， SJGB groups demonstrated a significant decrease in expiratory time （Te）， along with increases in peak expiratory flow （PEF）， 50% expiratory flow （EF50）， tidal volume （TV）， and expiratory volume （EV） （P<0.05）. High-dose SJGB ameliorated pathological changes in the lung tissue， reduced peribronchial inflammation scores， and decreased mean linear intercept （MLI） （P<0.01）. Compared with the model group， medium- and high-dose SJGB groups showed reductions in interleukin-6 （IL-6） and interleukin-1β （IL-1β） levels （P<0.01）. UHPLC-MS/MS revealed that the five most abundant components in SJGB were （S）-actinidine， ephedrine， pyroglutamic acid， methylephedrine， and coumarin. Transcriptomic analysis revealed 219 DEGs regulated by SJGB， suggesting that the anti-COPD effects of SJGB may be mediated through key genes such as cluster of differentiation 68 （CD68）， integrin subunit alpha X （ITGAX）， and cathepsin S （CTSS）， primarily involved in the lysosomal pathway. Western blot and Real-time PCR results confirmed that SJGB inhibited the expression of CD68， ITGAX， and CTSS compared with the model group （P<0.05）. ConclusionSJGB effectively improved the lung function and attenuated lung tissue inflammation in the mouse model of COPD by modulating the lysosomal pathway and related genes including CD68， ITGAX， and CTSS.
