Therapeutic Mechanisms of Xiebai San on Lung Heat-induced Cough and Asthma via Modulating Lung-Brain Axis Metabolism Based on Spatial Metabolomics

XU Yue; MA Fuzhi; AYIMAN Yeerjiang; ZHU Lin; ZANG Qingce; MA Zhijie

doi:10.13422/j.cnki.syfjx.20251701

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Therapeutic Mechanisms of Xiebai San on Lung Heat-induced Cough and Asthma via Modulating Lung-Brain Axis Metabolism Based on Spatial Metabolomics

更新时间：2026-01-07

- Therapeutic Mechanisms of Xiebai San on Lung Heat-induced Cough and Asthma via Modulating Lung-Brain Axis Metabolism Based on Spatial Metabolomics
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 32, Issue 3, Pages: 41-48(2026)
- 作者机构：
  
  1.首都医科大学附属北京地坛医院，北京 100015
  2.中国医学科学院北京协和医学院药物研究所，天然药物活性物质与功能国家重点实验室，北京 100050
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20251701
  CLC： R289;R259;R285
- Received：30 April 2025，
  
  Revised：2025-08-11，
  
  Accepted：13 August 2025，
  
  Published Online：28 August 2025，
  
  Published：05 February 2026
- 稿件说明：
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许悦,马富智,阿依曼·叶尔江等.空间代谢组学揭示泻白散改善肺-脑轴代谢治疗肺热咳喘[J].中国实验方剂学杂志,2026,32(03):41-48.

XU Yue,MA Fuzhi,AYIMAN Yeerjiang,et al.Therapeutic Mechanisms of Xiebai San on Lung Heat-induced Cough and Asthma via Modulating Lung-Brain Axis Metabolism Based on Spatial Metabolomics[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(03):41-48.
许悦,马富智,阿依曼·叶尔江等.空间代谢组学揭示泻白散改善肺-脑轴代谢治疗肺热咳喘[J].中国实验方剂学杂志,2026,32(03):41-48. DOI： 10.13422/j.cnki.syfjx.20251701.

XU Yue,MA Fuzhi,AYIMAN Yeerjiang,et al.Therapeutic Mechanisms of Xiebai San on Lung Heat-induced Cough and Asthma via Modulating Lung-Brain Axis Metabolism Based on Spatial Metabolomics[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(03):41-48. DOI： 10.13422/j.cnki.syfjx.20251701.

摘要

目的

基于整体动物质谱成像技术，采用空间代谢组学原位表征肺热咳喘模型及泻白散治疗后大鼠肺部及脑部代谢改变规律。

方法

将9只SD大鼠随机分为空白组（生理盐水）、模型组（生理盐水）、泻白散组（9 g·kg

-1

），每组3只。其中，模型组与泻白散给药组均采用脂多糖-卵清蛋白（LPS-OVA）诱导建立哮喘大鼠模型。泻白散治疗后，第21天将动物安乐死，并保持形态液氮速冻定形。利用冷冻切片机获取整体动物切片，并利用空气动力辅助解吸电喷雾离子化质谱成像（AFADESI-MSI）平台进行成像。对应光学成像图，提取出各组大鼠肺部及脑组织代谢物离子数据，并利用SIMCA、GrapPad Prism 9.0等软件对差异代谢物进行分析，根据HMDB（

https：//hmdb.ca/

https://hmdb.ca/

）及Lipd MAPS

（

https：//www.lipidmaps.org/

https://www.lipidmaps.org/

）数据库对差异代谢物进行鉴定，对肺部和脑部代谢改变进行分析。

结果

质谱成像结果显示，泻白散干预后，甘草中的新甘草素、甘草素等成分及地骨皮中的棕榈酰胺等成分在大鼠肺部和脑组织中有显著分布。对肺部分析结果表明，具有抗炎作用的物质，如柠檬酸显著下降（

0.01），溶血磷脂酰乙醇胺（LPE，17：1）、LPE（22：4）、LPE（19：0）（

0.01）等脂质代谢物显著上升，肺部炎症反应显著，泻白散干预后具有较好的改善作用。对脑组织中代谢改变进行分析，与空白组比较，模型组大鼠脑部氨基酸和脂肪酸代谢途径发生限制改变，其中，天冬氨酸、谷氨酸、脂肪酸（FA，18：5）、羟基脂肪酸（FAHFA，36：0；O）、FA（6：1；O6）及LPE（18：1）等物质上升，FA（16：0）和FA（20：4）等物质显著下降，泻白散给药后改善了脑部代谢异常。系统性分析肺热咳喘大鼠肺部及脑部代谢改变，结果表明，具有抗氧化性的不饱和磷脂类物质在模型组显著下降，提示肺热咳喘发生后氧化应激及炎症的的肺-脑轴反应。

结论

采用整体动物质谱成像空结合间代谢组学原位揭示了泻白散药物成分的体内分布，表征了肺热咳喘引起的肺部和脑部代谢改变，系统展示了肺-脑轴炎症反应及泻白散对其调控效果，为肺热咳喘中药研究提供有用信息。

Abstract

Objective

Based on whole-animal mass spectrometry imaging technology， spatial metabolomics was used to characterize

in situ

the metabolic alteration patterns in the lungs and brain of a rat model of lung heat-induced cough and asthma， as well as after treatment with Xiebai San.

Methods

Nine Sprague-Dawley （SD） rats were randomly divided into a blank group （physiological saline）， a model group （physiological saline）， and a Xiebai San group （9 g·kg

-1

）， with three rats in each group. The model group and the Xiebai San group were both induced using lipopolysaccharide-ovalbumin （LPS-OVA） to establish an asthma rat model. After treatment with Xieb

ai San， the animals were euthanized on day 21 and rapidly frozen in liquid nitrogen to preserve morphology. Whole-animal tissue sections were prepared using a cryomicrotome， and imaging was performed using the Air-flow-assisted Desorption Electrospray Ionization Mass Spectrometry Imaging （AFADESI-MSI） platform. Based on the corresponding optical images， ion data of metabolites from the lung and brain tissues of each group were extracted. Differential metabolites were analyzed using SIMCA and GraphPad Prism 9.0 software. Metabolites were identified using the HMDB （

https：//hmdb.ca/

https://hmdb.ca/

） and LipidMAPS

（

https：//www.lipidmaps.org/

https://www.lipidmaps.org/

） databases， and metabolic changes in the lungs and brain were analyzed.

Results

Mass spectrometry imaging showed that， after Xiebai San intervention， components such as neoglycyrrhizin and glycyrrhizin from Glycyrrhizae Radix et Rhizoma， as well as palmitamide from Lycii Cortex， were significantly distributed in the lung and brain tissues of rats. Lung analysis indicated that substances with anti-inflammatory effects， such as citric acid， were significantly decreased （

0.01）， while lipid metabolites such as lysophosphatidylethanolamine （LPE 17：1）， LPE （22：4）， and LPE （19：0）（

0.01） were significantly increased， showing a marked inflammatory response in the model group. After Xiebai San intervention， these conditions were notably improved. Analysis of metabolic changes in brain tissue showed that， compared with the blank group， amino acid and fatty acid metabolic pathways in the model group exhibited restricted alterations. Among them， levels of aspartic acid， glutamic acid， fatty acid （FA 18：5）， hydroxy fatty acids （FAHFA 36：0；O）， FA （6：1；O6）， and LPE （18：1） increased， whereas FA （16：0） and FA （20：4） significantly decreased. Administration of Xiebai San improved these me

tabolic abnormalities in the brain. Systematic analysis of lung and brain metabolic changes in rats with lung heat-induced cough and asthma showed that antioxidant unsaturated phospholipid substances were significantly decreased in the model group， suggesting oxidative stress and inflammation-related lung-brain axis responses after the onset of lung heat-induced cough and asthma.

Conclusion

Using whole-animal mass spectrometry imaging combined with spatial metabolomics revealed the

in vivo

distribution of Xiebai San constituents， characterized the metabolic alterations in the lungs and brain caused by lung heat-induced cough and asthma， and systematically demonstrated the lung-brain axis inflammatory responses and the regulatory effects of Xiebai San. These findings provide valuable information for the study of Chinese medicine in lung heat-induced cough and asthma.

关键词

Keywords

references

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