Effect of <italic style="font-style: italic">Yupingfeng Granules </italic>（玉屏风颗粒） on Metabonomics of Alveolar Lavage Fluid and Gut Microflora in  Chronic Obstructive Pulmonary Disease Model Rats

LIU Haiye; LUO shan; JIA Zhiling; DONG Wenjun; WANG Yuanyuan; WANG Jiepeng; YU Wentao

doi:10.13288/j.11-2166/r.2023.20.012

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Effect of Yupingfeng Granules （玉屏风颗粒） on Metabonomics of Alveolar Lavage Fluid and Gut Microflora in Chronic Obstructive Pulmonary Disease Model Rats

更新时间：2023-10-12

- Effect of Yupingfeng Granules （玉屏风颗粒） on Metabonomics of Alveolar Lavage Fluid and Gut Microflora in Chronic Obstructive Pulmonary Disease Model Rats
- Journal of Traditional Chinese Medicine Vol. 64, Issue 20, Pages: 2116-2124(2023)
- 作者机构：
  
  河北中医学院，河北省石家庄市杏苑路3号，050200
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2023.20.012
  CLC：
- Received：09 December 2022，
  
  Revised：2023-08-22，
  
  Published：17 October 2023
- 稿件说明：
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刘海叶,骆姗,贾智玲等.玉屏风颗粒对慢性阻塞性肺疾病模型大鼠肺泡灌洗液代谢组学及肠道菌群的影响[J].中医杂志,2023,64(20):2116-2124.

LIU Haiye,LUO shan,JIA Zhiling,et al.Effect of Yupingfeng Granules （玉屏风颗粒） on Metabonomics of Alveolar Lavage Fluid and Gut Microflora in Chronic Obstructive Pulmonary Disease Model Rats[J].Journal of Traditional Chinese Medicine,2023,64(20):2116-2124.
刘海叶,骆姗,贾智玲等.玉屏风颗粒对慢性阻塞性肺疾病模型大鼠肺泡灌洗液代谢组学及肠道菌群的影响[J].中医杂志,2023,64(20):2116-2124. DOI： 10.13288/j.11-2166/r.2023.20.012.

LIU Haiye,LUO shan,JIA Zhiling,et al.Effect of Yupingfeng Granules （玉屏风颗粒） on Metabonomics of Alveolar Lavage Fluid and Gut Microflora in Chronic Obstructive Pulmonary Disease Model Rats[J].Journal of Traditional Chinese Medicine,2023,64(20):2116-2124. DOI： 10.13288/j.11-2166/r.2023.20.012.

摘要

目的

从“肺-肠轴”角度探讨玉屏风颗粒防治慢性阻塞性肺疾病（COPD）的可能作用机制。

方法

32只大鼠随机分为正常组、模型组、罗红霉素组、玉屏风颗粒组，每组8只。除正常组外，其余各组大鼠采用气管滴注脂多糖（LPS）联合烟熏法制备COPD大鼠模型，持续12周。造模第5～12周，罗红霉素组和玉屏风颗粒组分别给予相应药物31.5 mg/（kg·d）、1.575 g/（kg·d）灌胃，正常组和模型组给予10 ml/（kg·d）生理盐水。末次给药后24 h取材。HE染色观察各组大鼠肺组织病理形态改变情况。正常组、模型组及玉屏风颗粒组大鼠应用超高效液相色谱-四极杆飞行时间质谱联用技术（UHPLC-QTOFMS）检测肺泡灌洗液（BALF）差异性代谢物；16S rDNA测序技术检测肠道菌群的差异菌属，并将差异性代谢物和差异菌属进行关联分析。

结果

与正常组比较，模型组大鼠小支气管壁杯状细胞增多，支气管壁平滑肌层消失，可见炎性细胞浸润；与模型组比较，罗红霉素组肺泡间质轻微水肿，炎性细胞明显减少；玉屏风颗粒组未见明显肺泡间质水肿，伴有少量炎性细胞浸润。BALF差异性代谢物筛选结果显示，与正常组比较，模型组中12种物质上调，19种物质下调；与模型组比较，玉屏风颗粒组中37种物质上调，43种物质下调。KEGG分析共得出2条代谢通路，分别是甘油磷脂代谢、不饱和脂肪酸的生物合成代谢；与模型组比较，玉屏风颗粒组胆碱、乙酰胆碱、甘油-3-磷酸、甘油磷酸胆碱、棕榈酸、花生四烯酸呈上升趋势；硬脂酸、二十二碳六烯酸呈下降趋势（

＜0.05）。肠道菌群结果显示，正常组和模型组有80种差异物种，模型组和玉屏风颗粒组有65种差异物种；与模型组比较，玉屏风颗粒组相对丰度水平前五位的物种中普雷沃菌属_9、Ruminococcaceae_UCG-005、Ruminiclostridium_6水平升高，乳杆菌属、拟杆菌属水平降低（

＜0.05）。相关性分析结果显示，模型组vs正常组，花生四烯酸与Oribacterium呈负相关（r=-0.753，

＜0.01）；玉屏风颗粒组vs模型组，硬脂酸与拟杆菌属（r=0.788）、分枝杆菌属（r=0.826）、［Eubacterium］_ruminantium_group（r=0.770）均呈正相关（

＜0.01）；花生酸与Roseiarcus（r=-0.779）、甘油-3-磷酸与脱硫弧菌属（r=-0.758）、花生四烯酸与Oribacterium（r=-0.753）、棕榈酸与Pseudolabrys（r=-0.750）均呈负相关（

＜0.01）。

结论

玉屏风颗粒可影响COPD模型大鼠BALF代谢产物和肠道微生物的菌群结构，调节“肺-肠轴”平衡可能是其防治COPD的可能作用机制之一。

Abstract

Objective

To explore the possible mechanism of

Yupingfeng Granules

（玉屏风散） in preventing and treating chronic obstructive pulmonary disease （COPD） from the perspective of “lung-gut axis”.

Methods

Thirty-two male Wistar rats were randomly divided into normal group，model group， roxithromycin group and

Yupingfeng Granules

group， with 8 rats in each group. Except for the normal group， the rat model of COPD was prepared by intratracheal instillation of lipopolysaccharide （LPS） combined with smoking for 12 weeks. Since the fifth week of modeling，the roxithromycin group and the

Yupingfeng Granules

group were given 31.5 mg/（kg·d） and 1.575 g/（kg·d） of corresponding drugs respectively by gavage，and normal group and model group were given 10 ml/（kg·d） physiolo-gical saline. Sample was collected 24 hours after the last administration. The pathological changes of lung tissue were observed using HE staining； Ultrahigh performance liquid chromatography quadrupole time of flight mass spectrometry （UHPLC-QTOFMS） was used to detect the differential metabolites in alveolar lavage fluid （BALF） in all groups but roxithromycin group；16S rDNA sequencing technology was used to detect the changes of intestinal flora， and the association analysis was conducted between the differential metabolites and the differential flora.

Results

Compared with the normal group， the model group showed an increase in goblet cells in the small bronchial wall， disappearance of the smooth muscle layer of the bronchial wall， and infiltration of inflammatory cells； compared with the model group， roxithromycin group showed slight alveolar interstital edema， and obviously reduced inflammatory cell， while no obvious alveolar interstital edema was observed in the

Yupingfeng Granules

group， showing a small amout of inflammatory cell infiltration. The results of the BALF differential metabolite screening showed that compared with the normal group， 12 substances were upregulated and 19 substances were downregulated in the model group； compared with the model group， 37 substances in the

Yupingfeng Granules

group were upregulated and 43 substances were downregulated KEGG analysis yielded a total of 2 metabolic pathways， glycerophospholipid metabolism， and unsaturated fatty acid biosynthetic metabolism； compared with the model group， choline， acetylcholine， glycerol-3-phosphate， glycerophosphate choline， palmitic acid， and arachidonic acid showed an upward trend， while stearic acid and docosahexaenoic acid showed a downward trend in

Yupingfeng Granules

group （

＜0.05）. The results of the intestinal flora showed that， there are 80 different species between the normal group and the model group， and 65 different species between the model group and

Yupingfeng Granules

group. Among the top 5 species with relative abundance levels，compared with the model group， the level of Prevotella_9，Ruminococcaceae_UCG-005，Ruminiclostridium_6 increase，and Lactobacillus，Bacteroides decrease（

＜0.05）.The results of the correlation analysis showed that， in the normal and model groups， arachidonic acid was negatively correlated with Oribacterium（r=

0.753，

＜0.01）； in the

Yupingfeng Granules

group and model group， stearic acid and Bacteroides（r=0.788）， Mycobacterium（r=0.826），［Eubacterium］_Ruminantium_Group（r=0.770） was positively correlated（

＜0.01）， Arachidic acid was negatively correlated with Roseiarcus（r=

0.779）， glycerol-3-phosphate was negatively correlated with Desulfovibrio（r=

0.758）， Arachidonic acid was negatively correlated with Oribacterium（r=

0.753）， and Palmitic acid was negatively correlated with Pseudolabs（r=

0.750，

＜0.01）.

Conclusion

Yupingfeng Granules

can affect the metabolism of BALF and the flora structure of intestinal microorganisms， and regulating the balance of “lung-gut axis” may be one of the mechanisms of

Yupingfeng Granules

in treatment of COPD.

关键词

Keywords

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Effect of Yupingfeng Granules （玉屏风颗粒） on Metabonomics of Alveolar Lavage Fluid and Gut Microflora in Chronic Obstructive Pulmonary Disease Model Rats

DOI：10.13288/j.11-2166/r.2023.20.012

摘要

Abstract

关键词

Keywords

references