基于代谢组学探究荆防颗粒改善空气细颗粒物诱导的大鼠肺损伤的作用机制OA

Objective To investigate the ameliorative effect of Jingfang granules on lung injury induced by ambient fine particulate matter(PM2.5)in rats and its potential mechanism of action.Methods Thirty clean-grade male Wistar rats were divided into three groups by random number table method:the control group,the model group,and the Jingfang granule group,with 10 rats in each group.Rats in the model group received an intratracheal instillation of 7.5 mg/kg PM2.5 suspension on the first day of each week,for a total of 4 times.Rats in the Jingfang granule group received daily intragastric administration of 1 340 mg/kg Jingfang granule suspension for 4 weeks,and on the first day of each week,they also received an intratracheal instillation of 7.5 mg/kg PM2.5 suspension,for a total of 4 times.HE staining was used to observe histopathological changes in lung tissue under the light microscope.Enzyme-linked immunosorbent assay was used to detect the serum interleukin(IL)-6,tumor necrosis factor-α(TNF-α),and IL-10 level.The qualitative and quantitative analysis of metabolites was performed using liquid chromatography-tandem mass spectrometry,and differential metabolite screening was conducted with R language screen,and pathway enrichment analysis of the differential metabolites was performed using the KEGG database.Results Observation under light microscopy showed that in the model group,the lung tissue exhibited obvious structural disorder,thickened alveolar walls,and abundant inflammatory exudates and red blood cells in the alveolar spaces,accompanied by extensive inflammatory cells infiltration including neutrophils and macrophages.In the Jingfang granule group,the pathological lung injury was significantly alleviated compared with the model group,with essentially intact alveolar structure,mildly widened alveolar septa,markedly reduced inflammatory cells infiltration,and relieved exudate,hyperemia,and edema in the alveolar spaces.Serum IL-6 and TNF-α levels in the model group were higher than those in the control group,while serum IL-10 level was lower than that in the control group(P<0.05).Serum IL-6 and TNF-α levels in the Jingfang granule group were lower than those in the model group,and serum IL-10 level was higher than that in the model group(P<0.05).A total of 44 differential metabolites were screened.KEGG pathway enrichment analysis results showed that three signaling pathways were mainly involved:folate biosynthesis pathway,the oxytocin signaling pathway,and carbon metabolism signaling pathway.Among these pathways,4 key differential metabolites were identified:tetrahydrosarcinapterin,cyclic ADP ribose,trimethylamine,and 4-(β-D-ribofuranosyl)aniline-5'-phosphate.Conclusion Jingfang granules can ameliorate lung injury induced by PM2.5 and reduce the inflammatory response in rats.The mechanism of action may be related to folate biosynthesis pathway,the oxytocin signaling pathway,and carbon metabolism signaling pathway.