基于代谢组学四妙勇安汤治疗糖尿病足的作用机制研究

doi:10.12114/j.issn.1007-9572.2024.0676

中国全科医学 ›› 2025, Vol. 28 ›› Issue (30): 3796-3805.DOI: 10.12114/j.issn.1007-9572.2024.0676

所属专题：内分泌代谢性疾病最新文章合辑

• 论著·中医·中西医结合研究 • 上一篇下一篇

基于代谢组学四妙勇安汤治疗糖尿病足的作用机制研究

张可兴¹, 张博²^,^*(), 吴琼¹, 朱珊珊¹, 王迪¹, 张春男¹

1．150036　黑龙江省哈尔滨市，黑龙江省医院药学部
2．150040　黑龙江省哈尔滨市，黑龙江中医药大学附属第二医院药剂科

收稿日期:2025-02-14 修回日期:2025-05-26 出版日期:2025-10-20 发布日期:2025-08-18
通讯作者: 张博
本文首次刊登于Precision Medication 2025年第2期（https://doi.org/10.1016/j.prmedi.2025.100028）

作者贡献：
张可兴提出研究思路，设计实验方案；张博负责网络药理学的整个实验方案的书写和论文的书写；吴琼负责利用TCMSP、GeneCards、OMIM、TTD软件进行网络药理学的具体数据分析和试验绘图；朱珊珊、王迪负责血清代谢组学中的血清样本收集和血清的处理和操作；张春男负责血清样本的收集及试验数据的处理分析。
基金资助:
黑龙江省中医管理局中医药科研课题(ZHY2022-066)

Research on the Mechanism of Action of Simiao Yongan Decoction in the Treatment of Diabetic Foot Based on Metabolomics

ZHANG Kexing¹, ZHANG Bo²^,^*(), WU Qiong¹, ZHU Shanshan¹, WANG Di¹, ZHANG Chunnan¹

1. Department of Hospital Pharmacy, Heilongjiang Province Hospital, Harbin 150036, China
2. Department of Pharmacy, the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, China

Received:2025-02-14 Revised:2025-05-26 Published:2025-10-20 Online:2025-08-18
Contact: ZHANG Bo

分享到

摘要/Abstract

摘要： 背景糖尿病足是糖尿病患者致残、致死的重要原因。随着时代和科技的进步，现代医学及中医学对于糖尿病足的认识及研究逐渐深入，进一步提高了糖尿病足的治疗手段，在一定程度上可以缓解疾病痛楚，改善患者的生活质量。目的运用代谢组学与网络药理学相结合的方法探讨四妙勇安汤治疗糖尿病足的作用机制。方法选取2023年7月—2024年8月于黑龙江省医院烧伤科、血管外科、南岗院区血管外科住院的糖尿病足患者为研究对象。本研究共纳入符合标准热毒炽盛型糖尿病足患者60例。随机分成清创组、西药组、中药组、中西联用组，各组15例，另纳入同时期15例健康志愿者作为对照组。首先，运用TCMSP、GeneCards、OMIM、TTD等数据库和软件，寻找四妙勇安汤对糖尿病足的药效学基础、作用靶点及代谢通路。并将四妙勇安汤的血清代谢组学与网络药理学进行整合研究，验证四妙勇安汤干预糖尿病足可能的有效成分及代谢通路。结果四妙勇安汤治疗糖尿病足的主要活性成分为木犀草素、槲皮素和刺芒柄花素等；可能通过AKT1、TNF、HSP90AA1、MAPK8、STAT3等靶点，调控丝裂原活化蛋白激酶信号通路、肿瘤坏死因子信号通路、磷脂酰基醇信号通路、HIF-1信号通路、Toll样受体信号通路等途径治疗糖尿病足，其中磷脂酰基醇信号通路与四妙勇安汤血清代谢组学的研究结果一致。结论四妙勇安汤治疗糖尿病足的主要活性成分为木犀草素、槲皮素和刺芒柄花素等；磷脂酰肌醇信号通路可能是四妙勇安汤干预糖尿病足的代谢通路。

关键词: 糖尿病足, 四妙勇安汤, 代谢组学, 网络药理学, 代谢通路, 磷脂酰肌醇

Abstract:

Background

In recent years, diabetic foot has become an important cause of disability and death among diabetic patients. With the advancement of the times and technology, modern medicine and traditional Chinese medicine have gradually deepened their understanding and research on diabetic foot, further improving the treatment methods for diabetic foot. To a certain extent, this can relieve the pain of patients and improve their quality of life.

Objective

The mechanism of action of Simiao Yongan Decoction in the treatment of diabetic foot was explored by combining metabolomics with network pharmacology.

Methods

Diabetic foot patients who were hospitalized in the Burn Department, Vascular Surgery Department of Heilongjiang Provincial Hospital and the Vascular Surgery Department of Nangang Campus from July 2023 to August 2024 were selected as the research subjects. A total of 60 patients with heat-toxin intense diabetic foot who met the criteria were included in this study. They were randomly divided into debridement group, Western medicine group, traditional Chinese medicine group and combined Chinese and Western medicine group, with 15 cases in each group. Another 15 normal people were included as the control group. Firstly, databases and software such as TCMSP, GeneCards, OMIM, and TTD were used to search for the pharmacodynamic basis, target sites and metabolic pathways of Simiao Yongan Decoction on diabetic foot. The serum metabolomics and network pharmacology of Simiao Yongan Decoction were integrated for research to verify the possible active ingredients and metabolic pathways of Simiao Yongan Decoction in the intervention of diabetic foot.

Results

The main active ingredients of Simiao Yongan Decoction for treating diabetic foot are luteolin, quercetin and acanthopanthin, etc. Diabetic foot may be treated by regulating pathways such as mitogen-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, phosphatidyacyl alcohol signaling pathway, HIF-1 signaling pathway, and Toll-like receptor signaling pathway through targets such as AKT1, TNF, HSP90AA1, MAPK8, and STAT3. Among them, the phospholipacyl alcohol signaling pathway is consistent with the research results of the serum metabolomics of Simiao Yongan Decoction.

Conclusion

The main active ingredients of Simiao Yongan Decoction for treating diabetic foot are luteolin, quercetin and acanthopanthin, etc. The phosphatidylinositol signaling pathway may be the one through which Simiao Yongan Decoction interferes with the metabolism of diabetic foot.

Key words: Diabetic foot, Simiao Yongan Decoction, Metabolomics, Network pharmacology, Metabolic pathway, Phosphatidyl inositol

中图分类号:

R 587.29

张可兴,张博,吴琼,等. 基于代谢组学四妙勇安汤治疗糖尿病足的作用机制研究[J]. 中国全科医学, 2025, 28(30): 3796-3805. DOI: 10.12114/j.issn.1007-9572.2024.0676.
ZHANG Kexing,ZHANG Bo,WU Qiong, et al. Research on the Mechanism of Action of Simiao Yongan Decoction in the Treatment of Diabetic Foot Based on Metabolomics[J]. Chinese General Practice, 2025, 28(30): 3796-3805. DOI: 10.12114/j.issn.1007-9572.2024.0676.

图/表 10

表1 研究使用的数据库、平台与软件

Table 1 The database，platform and software used in the research

名称	版本	网址
TCMSP数据库^[7]	2.3	https://tcmspw.com/tcmsp.php
Uniprot数据库^[8]		https://www.uniprot.org
GeneCards数据库^[9]		http://www.genecards.org/
OMIM数据库^[10]		https://omim.org
TTD数据库^[11]		http://db.idrblab.net/ttd/
String平台^[12]	11b	https://string-db.org
Metascape平台^[13]		https://metascape.org
PDB数据库^[14]		https://www.rcsb.org
Cytoscape^[15]	3.8.0
AutoDockTools	1.5.6
Pymol
RStudio
Discovery Studio	4.5

表2 血清代谢组学洗脱梯度

Table 2 Serum metabolomics elution gradient

时间（min）	流速（mL/min）	%A相（0.1%甲酸-乙腈）	%B相（0.1%甲酸-水）
Initial	0.400	1.0	99.0
0.50	0.400	20.0	80.0
2.50	0.400	60.0	40.0
4.00	0.400	66.0	34.0
5.00	0.400	80.0	20.0
7.50	0.400	86.0	14.0
8.00	0.400	99.0	1.0
9.00	0.400	99.0	1.0

图1 四妙勇安汤治疗DF的PPI网络注：圆点由小到大、颜色由浅到深表示靶点的度值（Degree）增大。

Figure 1 The PPI network of Simiao Yongan Decoction in the treatment of DF

图2 "中药-药效物质-潜在靶点"网路注：圆形节点为潜在靶点，菱形节点为中药，六边形节点为有效成分；蓝色代表靶点，青色代表玄参，黄色代表金银花，紫色代表当归，褐色代表甘草，红色代表共有成分。

Figure 2 ＂Traditional Chinese Medicine-Active Substances-Potential Targets＂ network

图3 GO富集及KEGG Pathway富集分析注：A为GO-MF富集试验，B为GO-BP富集试验，C为GO-CC富集试验，D为KEGG富集试验。

Figure 3 GO enrichment and KEGG Pathway enrichment analysis

图4 四妙勇安汤干预DF患者血清代谢轮廓注：A为对照组、清创组和治疗前血清代谢轮廓，B为对照组、西药组和治疗前血清代谢轮廓，C为对照组、中药组和治疗前血清代谢轮廓，D为对照组、中西联用组和治疗前血清代谢轮廓；E为对照组、西药组、治疗前和中西联用组血清代谢轮廓。

Figure 4 The Simiao Yongan Decoction intervened in the serum metabolic profile of patients with DF

图5 四妙勇安汤干预DF患者血清生物标志物层次聚类热图注：K=对照组，Q=清创组，X=西药组，Z=中药组，ZLQ=治疗前，ZX=中西联用组。

Figure 5 Hierarchical clustering heat map of serum biomarkers in patients with DF intervened by Simiao Yongan Decoction

图6 四妙勇安汤干预DF患者血清生物标志物相对峰面积注：K=对照组，ZLQ=治疗前，ZX=中西联用组

Figure 6 The relative peak area of serum biomarkers in patients with DF intervened by Simiao Yongan Decoction

表3 四妙勇安汤干预DF患者代谢物参与代谢通路情况

Table 3 The participation of metabolites in metabolic pathways of patients with diabetic foot in the intervention of Simiao Yongan Decoction

代谢途径	原始P值	错误发现率	影响力
甘油磷脂代谢	0.013 454	0.643 01	0.244 36
嘧啶代谢	0.015 701	0.643 01	0.068 09
氮代谢	0.030 620	0.643 01	0
D-谷氨酰胺和D-谷氨酸代谢	0.030 620	0.643 01	0.500 00
糖基磷脂酰肌醇（GPI）锚生物合成	0.070 168	0.745 10	0.003 99
精氨酸生物合成	0.070 168	0.745 10	0.116 75
丁酸代谢	0.075 011	0.745 10	0
组氨酸代谢	0.079 832	0.745 10	0
甘油酯代谢	0.079 832	0.745 10	0.012 46
泛酸和辅酶A（CoA）的生物合成	0.094 163	0.755 20	0.235 71
醚脂代谢	0.098 896	0.755 20	0.144 58
磷脂酰肌醇信号系统	0.135 990	0.808 66	0.001 52
谷胱甘肽代谢	0.135 990	0.808 66	0.019 66
丙氨酸、天冬氨酸和谷氨酸代谢	0.135 990	0.808 66	0.197 12
卟啉和叶绿素代谢	0.145 050	0.808 66	0
乙醛酸盐和二羧酸盐代谢	0.154 030	0.808 66	0
精氨酸和脯氨酸代谢	0.180 470	0.891 75	0.086 00
氨酰基转移核糖核酸生物合成	0.222 940	1.000 00	0
嘌呤代谢	0.290 730	1.000 00	0

图7 四妙勇安汤干预DF患者代谢物参与代谢通路情况

Figure 7 The participation of metabolites in metabolic pathways of patients with DF in the intervention of Simiao Yongan Decoction

参考文献 16

[1]	中国医疗保健国际交流促进会糖尿病足病分会，国际血管联盟中国分部糖尿病足病专家委员会. 中国糖尿病足诊治指南[J]. 中国临床医生杂志，2020,6(1):19-27.
[2]	甘兆义，李春妮，韦雄丽，等. 糖尿病周围神经病变的早期诊断及治疗进展[J]. 中国卫生标准管理，2023,14(11):194-198. DOI：10.3969/j.issn.1674-9316.2023.11.042.
[3]	张可兴. 四妙勇安汤治疗热毒炽盛型糖尿病足临床及代谢组学研究[D]. 哈尔滨：黑龙江中医药大学，2021.
[4]	赵益，王林华，廖怀章，等. 基于网络药理学及分子对接探讨四妙勇安汤治疗糖尿病足的作用机制[J]. 湖南中医杂志，2023,39(8):166-173. DOI：10.16808/j.cnki.issn1003-7705.2023.08.039.
[5]	韩松林. 中医综合外治法治疗糖尿病足溃疡期疗效观察[J]. 实用中医药杂志，2019,35(5):612-613.
[6]	揭珊珊，刘建鑫，于峥，等. 四妙勇安汤抗炎机制的研究进展[J]. 中国中医基础医学杂志，2022,28(9):1539-1542. DOI：10.19945/j.cnki.issn.1006-3250.20211109.001.
[7]	RU J L, LI P, WANG J N，et al. TCMSP：a database of systems pharmacology for drug discovery from herbal medicines[J]. J Cheminform，2014,6:13. DOI：10.1186/1758-2946-6-13.
[8]	CONSORTIUM U. UniProt：the universal protein knowledgebase in 2021[J]. Nucleic Acids Res，2021,49(D1):D480-489. DOI：10.1093/nar/gkaa1100.
[9]	SAFRAN M, DALAH I, ALEXANDER J，et al. GeneCards Version 3：the human gene integrator[J]. Database（Oxford），2010,2010:baq020. DOI：10.1093/database/baq020.
[10]	AMBERGER J S, HAMOSH A. Searching online mendelian inheritance in man（OMIM）：a knowledgebase of human genes and genetic phenotypes[J]. Curr Protoc Bioinformatics，2017,58:1.2.1-1.2.1.2.12. DOI：10.1002/cpbi.27.
[11]	WANG Y X, ZHANG S, LI F C，et al. Therapeutic target database 2020：enriched resource for facilitating research and early development of targeted therapeutics[J]. Nucleic Acids Res，2020,48(D1):D1031-1041. DOI：10.1093/nar/gkz981.
[12]	SZKLARCZYK D, FRANCESCHINI A, WYDER S，et al. STRING v10：protein-protein interaction networks，integrated over the tree of life[J]. Nucleic Acids Res，2015,43(Database issue):D447-452. DOI：10.1093/nar/gku1003.
[13]	ZHOU Y Y, ZHOU B, PACHE L，et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets[J]. Nat Commun，2019,10(1):1523. DOI：10.1038/s41467-019-09234-6.
[14]	BURLEY S K, BERMAN H M, KLEYWEGT G J，et al. Protein data bank（PDB）：the single global macromolecular structure archive[J]. Methods Mol Biol，2017,1607:627-641. DOI：10.1007/978-1-4939-7000-1_26.
[15]	SHANNON P, MARKIEL A, OZIER O，et al. Cytoscape：a software environment for integrated models of biomolecular interaction networks[J]. Genome Res，2003,13(11):2498-2504. DOI：10.1101/gr.1239303.
[16]	CHANG L, GRAHAM P H, NI J，et al. Targeting PI3K/Akt/mTOR signaling pathway in the treatment of prostate cancer radioresistance[J]. Crit Rev Oncol，2015,96(3):507-517. DOI：10.1016/j.critrevonc.2015.07.005.

基于代谢组学四妙勇安汤治疗糖尿病足的作用机制研究

Research on the Mechanism of Action of Simiao Yongan Decoction in the Treatment of Diabetic Foot Based on Metabolomics

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 10

参考文献 16

相关文章 15

编辑推荐

Metrics

留言

[1]	王爽, 吴树法, 令垚, 谭茜蔚, 曹汝岱, 曾慧婷, 孔丹莉, 丁元林, 于海兵. 基于代谢组学探究非脂质代谢物在肥胖与糖尿病视网膜病变间的中介作用：孟德尔随机化研究[J]. 中国全科医学, 2025, 28(21): 2625-2634.
[2]	张玉双, 吴忠冰, 黄鸣, 贾蕾, 高爽, 赵伟鹏, 李晶. 基于非靶代谢组学探究食管鳞状细胞癌津血亏虚证患者的代谢特征[J]. 中国全科医学, 2025, 28(12): 1513-1519.
[3]	岑妮秒, 韦云师, 黄丽娜, 吴标良. 外泌体微小RNA参与糖尿病足溃疡修复的研究进展[J]. 中国全科医学, 2025, 28(09): 1156-1160.
[4]	马晓萱, 王荣琦. 代谢组学在肝细胞癌诊疗中的研究进展[J]. 中国全科医学, 2025, 28(08): 1017-1022.
[5]	杨安银, 刘红丽, 陈妙洋, 郑玉凤, 徐志远, 杨永峰. 基于网络药理学方法探析汉黄芩素治疗肝细胞癌作用机制和体外实验研究[J]. 中国全科医学, 2024, 27(32): 4040-4049.
[6]	张林, 高锦, 吴明华, 王广梅. 通脑饮治疗急性脑梗死的临床疗效及作用机制研究：基于网络药理学和分子对接技术[J]. 中国全科医学, 2024, 27(23): 2904-2912.
[7]	武云凤, 骆燕洪, 蒋平南, 吴旻, 杨嘉, 阳琰, 陈霞, 蔡玉兰. 血清25羟维生素D₃水平与糖尿病足创面愈合相关性的巢式病例对照研究[J]. 中国全科医学, 2024, 27(15): 1811-1816.
[8]	刁翯, 白文佩, 赵立东. 左慈丸的化学成分及治疗围绝经期听力损失的作用机制研究：基于网络药理学与分子对接技术[J]. 中国全科医学, 2024, 27(12): 1493-1503.
[9]	林令君, 郭俊, 王俊伟, 高杨, 陈惠盈, 万永丽. 糖尿病足发病风险预测模型的系统评价[J]. 中国全科医学, 2024, 27(03): 357-363.
[10]	张康, 赵婷婷, 张波, 高梦琦, 李昱熹, 王邵鹏, 赵文景. 基于网络药理学探究布地奈德治疗IgA肾病的作用机制[J]. 中国全科医学, 2023, 26(35): 4453-4458.
[11]	张娟, 李海芬, 李小曼, 姚苗, 马惠珍, 马强. 糖尿病足溃疡复发风险预测模型的构建：基于Logistic回归和支持向量机及BP神经网络模型[J]. 中国全科医学, 2023, 26(32): 4013-4019.
[12]	董亚楠, 姜晓锐, 王凯, 宗传冲, 林国栋, 李香卿, 林春晓, 迟俊涛. 改良胫骨横向骨搬运技术治疗Wagner 3~4级糖尿病足患者的效果研究[J]. 中国全科医学, 2023, 26(27): 3411-3416.
[13]	王岗, 岳仁宋, 龚光明. 糖尿病足溃疡愈合后复发危险因素的病例对照研究[J]. 中国全科医学, 2023, 26(15): 1857-1862.
[14]	黄湘平, 吴玲, 谭超超. 基于液相色谱-串联质谱法的轻症和重症急性胰腺炎差异的血清代谢组学研究[J]. 中国全科医学, 2023, 26(09): 1118-1124.
[15]	吴文霞, 陈桂珊, 刘兴州, 尤丽丽, 刘丹, 严励. 基线老年营养风险指数对糖尿病足合并下肢动脉病变患者血管腔内治疗后临床结局的影响研究[J]. 中国全科医学, 2022, 25(36): 4496-4501.