基于临床代谢组学与蛋白质组学研究粉葛治疗轻度血脂异常的作用机制  

Mechanism of Puerariae Thomsonii Radix in treatment of mild dyslipidemia:based on clinical metabolomics and proteomics

作　　者：易建云 朱卫丰 管咏梅 周旭[3] 陈晓凡[3] 杨世林[1] 冯育林[1] 欧阳辉[1] YI Jian-yun;ZHU Wei-feng;GUAN Yong-mei;ZHOU Xu;CHEN Xiao-fan;YANG Shi-lin;FENG Yu-lin;OUYANG Hui(National Engineering Research Center for Manufacturing Technology of Solid Preparations of Traditional Chinese Medicine,Jiangxi University of Chinese Medicine,Nanchang 330006,China;Key Laboratory of Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Evidence-based Medicine Research Center,Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学中药固体制剂制造技术国家工程研究中心,江西南昌330006 [2]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004 [3]江西中医药大学循证医学研究中心,江西南昌330004

出　　处：《中国中药杂志》2024年第10期2818-2827,共10页China Journal of Chinese Materia Medica

基　　金：江西中医药大学科技创新团队计划项目(CXTD22001);中药材大品种粉葛多糖新功能因子的制备、评价与产业化研究项目(20223BBG71002);2022年国家青年岐黄学者项目。

摘　　要：研究粉葛临床上治疗轻度血脂异常潜在的代谢途径和作用靶点。采用UPLC-Q-TOF-MS和EASY-nLC-timsTOF-Pro2技术对轻度血脂异常患者在基线和服药12周后的血浆样品展开代谢组学和蛋白质组学研究。通过多元统计分析比较组间差异,并对轻度血脂异常密切相关的代谢物和蛋白与临床血脂指标分别进行相关性分析,结合基因本体(Gene Ontology,GO)功能分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析结果,绘制粉葛治疗轻度血脂异常可能的作用途径和靶点。结果显示,粉葛治疗后患者血浆中共有56个差异代谢物和78个差异蛋白产生回调效应,包括脂质和糖代谢相关的蛋白或代谢物(ApoB-100、9,10-DHOME、GAPDH、PGK1、PGAM1、ENO1等)、炎症与氧化应激相关的蛋白或代谢物(氧化磷脂、PLA2G7、LTA4H等)。结果表明,粉葛治疗轻度血脂异常的作用机制可能与下调ApoB-100的过表达、激活PPARα/γ、促进脂肪和甘油的分解、缓解LTB4与氧化磷脂介导的氧化应激密切相关。This study aims to explore the potential metabolic pathways and targets of Puerariae Thomsonii Radix in the clinical treatment of mild dyslipidemia.UPLC-Q-TOF-MS and EASY-nLC-timsTOF-Pro2 were employed to perform metabolomic and proteomic analyses of the plasma samples collected from the patients with mild dyslipidemia at baseline and after 12 weeks of treatment with Puerariae Thomsonii Radix.The multivariate statistical analysis was carried out for comparison between groups,and the correlation analysis was performed for the metabolites and proteins closely related to mild dyslipidemia with the blood lipid indexes.The possible pathways and targets for mitigating mild dyslipidemia were screened out by the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis.The results showed that 56 differential metabolites and 78 differential proteins in the plasma of patients were associated with Puerariae Thomsonii Radix treatment.In addition,changes were detected for the proteins or metabolites(ApoB-100,9,10-DHOME,GAPDH,PGK1,PGAM1,ENO1,etc.) involved in lipoprotein,lipid,and glucose metabolism and the proteins or metabolites(oxidized phospholipid,PLA2G7,LTA4H,etc.) related to inflammation and oxidative stress.Puerariae Thomsonii Radix may down-regulate the overexpression of ApoB-100,activate the peroxisome proliferator-activated receptor α/γ(PPARα/γ),promote the catabolism of fat and glycerol,and alleviate the oxidative stress mediated by oxidized phospholipids and leukotriene B4(LTB4) in the treatment of mild dyslipidemia.

关 键 词：粉葛 轻度血脂异常 代谢组学 蛋白质组学 脂质代谢 氧化应激 

分 类 号：R285[医药卫生—中药学]