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。
Mechanism of Puerariae Thomsonii Radix in treatment of mild dyslipidemia:based on clinical metabolomics and proteomics
This study aims to explore the potential metabolic pathways and targets of Puerariae Thomsonii Radix in the clinical treat-ment of mild dyslipidemia.UPLC-Q-TOF-MS and EASY-nLC-timsTOF-Pro2 were employed to perform metabolomic and proteomic ana-lyses 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 Ra-dix may down-regulate the overexpression of ApoB-100,activate the peroxisome proliferator-activated receptor α/γ(PPARα/γ),pro-mote 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.
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