基于代谢组学探讨桔梗汤对脂多糖诱导的小鼠急性肺损伤的保护作用

The effect of Jiegeng decoction on lipopolysaccharide-induced acute lung injury in mice based on metabolomics

桔梗汤作为治疗肺部疾病的经典方剂之一,其化学组成与作用机制尚不明确。本研究采用高分辨质谱技术检测桔梗汤中的化学成分,通过代谢组学技术探究桔梗汤对急性肺损伤(acute lung injury,ALI)模型小鼠肺组织代谢物的影响。以差异倍数(fold change,FC)>1.5或FC<0.67,并且P<0.05为条件筛选潜在生物标志物并进行代谢通路富集分析。桔梗汤经质谱分析共鉴定出40个化合物,包括三萜皂苷类成分、黄酮类成分、糖苷类成分等。动物实验经天津中医药大学实验动物伦理委员会批准(批准号:TCM-LAEC2021106)。研究发现,桔梗汤可改善ALI模型小鼠的肺系数及肺组织形态,降低肺泡灌洗液中丙二醛、肿瘤坏死因子-α、白介素-6的含量,减少肺组织中髓过氧化物酶含量。代谢组学结果表明,桔梗汤可调节与ALI相关的22个代谢物,其中白三烯D4、二十二碳五烯酸、次黄嘌呤、L-5-羟脯氨酸等代谢物主要与机体炎症反应和氧化应激相关,且被富集于谷胱甘肽代谢、嘌呤代谢和初级胆汁酸生物合成等通路。本研究通过代谢组学分析桔梗汤治疗ALI的潜在作用机制,为桔梗汤的临床应用提供了重要的理论依据。

One of the traditional prescriptions for treating lung diseases,Jiegeng decoction(JGT),is still unknown in terms of its chemical makeup and mechanism.In this study,Q-Exactive-Orbitrap MS technology was used to identify the chemical constituents of JGT,and metabolomics was used to examine the effect of JGT on metabolites in the lung tissue of mice with acute lung injury(ALI)model.The potential biomarkers were screened by fold change(FC)>1.5 or FC<0.67 and P<0.05,and enriched for metabolic pathways.A total of 40 compounds,including triterpenoid saponins,flavonoids and glycosides,were identified by mass spectrometry analysis of JGT.All animal experiments were approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine(No.TCM-LAEC2021106).The results showed that JGT improved the lung coefficient,and lung tissue morphology of mice with ALI,lowered the levels of malondialdehyde(MDA),tumor necrosis factorα(TNF-α),and interleukin 6(IL-6)in bronchoalveolar lavage fluid(BALF),and reduced myeloperoxidase(MPO)content in lung tissue.The metabolomic results showed that JGT could regulate 22 metabolites associated with ALI,among which leukotriene D4,docosapentaenoic acid,hypoxanthine,L-5-oxoproline,and other metabolites were mainly associated with the body′s inflammatory response and oxidative stress,and were enriched in the pathways of glutathione metabolism,purine metabolism,and primary bile acid biosynthesis.This study analyzed the potential mechanism of JGT in the treatment of ALI through metabolomics,providing an important theoretical basis for the clinical application of JGT.