Study on the protective effect of sesquiterpene lactones of Eupatorium lindleyanum DC.on lipopolysaccharide-induced acute lung injury in rats
10.13406/j.cnki.cyxb.003853
- VernacularTitle:野马追倍半萜内酯对脂多糖诱导大鼠急性肺损伤的保护作用研究
- Author:
Chen LUO
1
;
Yan YANG
;
Li LINGHU
;
Lian XIA
;
Keyun ZHOU
;
Chuanxin LIU
;
Xianqin LUO
Author Information
1. 重庆医科大学中医药学院,重庆 400016
- Keywords:
sesquiterpene lactones of Eupatorium lindleyanum DC.;
acute lung injury;
pulmonary barrier;
metabolomics
- From:
Journal of Chongqing Medical University
2025;50(7):889-897
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the protective effect of sesquiterpene lactones of Eupatorium lindleyanum DC.(SLEL)on lipopolysac-charide(LPS)-induced acute lung injury(ALI)in rats using metabolomics.Methods:Forty-eight male SD rats were randomly divided into a blank control group(CG),a model control group(MG),low-,medium-,and high-dose SLEL groups(50,100,and 200 mg/kg),and a positive control group(dexamethasone acetate tablets,5 mg/kg).CG and MG groups were given phosphate-buffered saline.All groups received intragastric administration at a dose volume of 10 mL/kg once a day for 7 consecutive days.One hour after the last ad-ministration,LPS(5 mg/kg)was instilled into the trachea of all groups except the CG group to establish the ALI rat model.Twenty-four hours after model establishment,blood was collected from the abdominal aorta and bronchoalveolar lavage fluid(BALF)was col-lected from the left lung.The total number of inflammatory cells,neutrophils,lymphocytes,and eosinophils in BALF was counted by Wright-Giemsa staining.The levels of interleukin-18(IL-18)and interferon-γ(IFN-γ)in serum and BALF were measured by enzyme-linked immunosorbent assay.The pathological changes of lung tissue were observed using hematoxylin-eosin staining.The ex-pression levels of tight junction protein-1(ZO-1)and occludin in lung tissue were determined by Western blot.The mRNA expression levels of IL-18,IFN-γ,ZO-1,and occludin in the lung were measured by real-time fluorescence quantitative PCR.Non-targeted me-tabolomics analysis of serum and lung tissue was performed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.Results:Compared with the MG group,all SLEL groups had significantly reduced wet/dry weight ratio of lung tissue,lung coefficient,and total number of inflammatory cells,neutrophils,lymphocytes,and eosinophils in BALF.SLEL signifi-cantly decreased the levels of IL-18 and IFN-γ in serum and BALF and the mRNA expression of IL-18 and IFN-γ in lung tissue,and significantly promoted the protein and mRNA expression of ZO-1 and occludin.Under light microscopy,the degree of lung tissue edema,alveolar hemorrhage,and inflammatory cell infiltration were significantly reduced,indicating a certain protective effect on ALI rats.The results of non-targeted metabolomics studies showed that there were 91 and 33 significantly different metabolites in the serum and lung tissue of rats treated with SLEL,respectively.Among them,the main differential metabolites in the serum were sphingosine,L-lactic acid,nicotinic acid,D-nucleotide,and mevalonate-5P,while the main differential metabolites in the lung tissue were tauro-cholic acid.This suggests that SLEL may mainly affect the metabolic pathways of sphingolipids,pyruvate,nicotinic acid,nicotinamide,and tryptophan in the serum and the metabolic pathways of taurine and hypotaurine in the lung tissue to improve ALI.Conclusion:SLEL has a significant protective effect on rats against LPS-induced ALI,and its mechanism of action may be related to the inhibition of inflammatory factors,improvement of lung barrier function,and regulation of related metabolic pathways.
