首页|基于尿液代谢组学和生物网络分析整合策略研究益肾固络合剂治疗慢性肾小球肾炎作用机制

基于尿液代谢组学和生物网络分析整合策略研究益肾固络合剂治疗慢性肾小球肾炎作用机制

Mechanism of Yishen Guluo Mixture in the Treatment of Chronic Glomerulonephritis:Based on Urine Metabolomics Combined with Biological Network Analysis

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目的:基于尿液代谢组学和生物网络分析整合策略研究益肾固络合剂治疗慢性肾小球肾炎(CGN)的关键代谢途径和潜在靶点.方法:建立阳离子化牛血清白蛋白(C-BSA)诱导的CGN大鼠模型,采用超高效液相色谱-质谱联用(UPLC-MS)代谢组学筛选益肾固络合剂治疗CGN的尿液内源性代谢标志物和代谢途径.整合生物网络分析工具对益肾固络合剂调节的生物标志物进行网络分析,挖掘益肾固络合剂治疗CGN的生物功能和潜在靶点.结果:基于尿液代谢组学技术筛选出花生四烯酸等20个益肾固络合剂治疗CGN的内源性代谢标志物.对益肾固络合剂调控的关键内源性代谢物生物网络分析结果表明,花生四烯酸代谢是益肾固络合剂发挥治疗CGN作用的潜在关键通路,其代谢途径上的细胞色素P450 4A11(CYP4A11)等10个靶点为益肾固络合剂治疗CGN的潜在靶点.结论:本研究初步揭示了益肾固络合剂治疗CGN的作用机制,为益肾固络合剂临床推广应用提供科学理论依据.
Objective:To explore the key metabolic pathways and potential targets of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN)based on the integrated strategy of urine metabolomics and biological network analysis.Meth-ods:The rat model of CGN was induced by cationic bovine serum albumin(C-BSA).The endogenous metabolic markers and meta-bolic pathways of Yishen Guluo Mixture in the treatment of CGN were screened by ultrahigh performance liquid chromatography-mass spectrometry(UPLC-MS)-based metabolomics.The biological network analysis tools were used to analyze the biomarkers reg-ulated by Yishen Guluo Mixture,from which the potential targets of Yishen Guluo Mixture in the treatment of CGN were mined.Re-sults:The urine metabolomics screened out 20 endogenous metabolic markers such as arachidonic acid in the treatment of CGN by Yishen Guluo Mixture.Further biological network analysis showed that arachidonic acid metabolism was a potential key pathway for Yishen Guluo Mixture in the treatment of CGN,and 10 molecules such as cytochrome P450 4A1 1(CYP4A11)in this pathway were potential targets for Yishen Guluo Mixture to treat CGN.Conclusion:This study preliminarily revealed the mechanism of Yishen Guluo Mixture in the treatment of CGN and provided a theoretical basis for the clinical application of Yishen Guluo Mixture.

Yishen Guluo MixtureChronic glomerulonephritisBiomarkersMetabolic pathwayMechanism of actionUrine metabolomicsBiological network analysisArachidonic acid metabolism

卞振华、张文明、唐静月、胡敏敏、陈晓伟、袁晓航、陆兔林

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南京中医药大学无锡附属医院,无锡,214071

南京中医药大学药学院,南京,210023

益肾固络合剂 慢性肾小球肾炎 生物标志物 代谢通路 作用机制 尿液代谢组学 生物网络分析 花生四烯酸代谢

国家自然科学基金面上项目江苏省研究生科研创新计划项目无锡市科技发展资金项目无锡市科技发展资金项目无锡市卫生健康委科研项目无锡市卫生健康委科研项目无锡市"双百"中青年医疗卫生拔尖人才培养计划项目

81873008KYCX20_1513N20202009N20192038MS2019412020ZHYB17HB2020059

2023

世界中医药
世界中医药学会联合会

世界中医药

CSTPCDCHSSCD北大核心
影响因子:1.266
ISSN:1673-7202
年,卷(期):2023.18(20)
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