药学学报, 2022, 57(4): 1115-1122
王艳霞, 沈霞*, 颜永刚*, 彭亮, 杨冰月, 平凡, 朱琳, 佘鑫华. 基于UHPLC-Q-TOF/MS的大黄治疗血瘀证的多元统计分析及代谢调控机制研究[J]. 药学学报, 2022, 57(4): 1115-1122.
WANG Yan-xia, SHEN Xia*, YAN Yong-gang*, PENG Liang, YANG Bing-yue, PING Fan, ZHU Lin, SHE Xin-hua. Research on multivariate statistical analysis and metabolic regulation mechanism of Rhei Radix et Rhizoma treating blood stasis syndrome based on UHPLC-Q-TOF/MS[J]. Acta Pharmaceutica Sinica, 2022, 57(4): 1115-1122.

王艳霞, 沈霞*, 颜永刚*, 彭亮, 杨冰月, 平凡, 朱琳, 佘鑫华
陕西中医药大学药学院, 陕西省秦岭中草药应用开发工程技术研究中心, 陕西 咸阳 712046
基于超高效液相色谱-四级杆飞行时间质谱仪(UHPLC-Q-TOF/MS)研究大黄治疗血瘀证的多元统计分析及代谢调控机制。本研究运用多元统计分析对血瘀证模型大鼠血浆样本中具有显著调节作用的代谢物进行差异特征综合分析,分析大黄调节血瘀证的差异代谢物的变化,并对已鉴定的代谢物进行通路富集分析。结果显示,模型组与对照组大鼠血浆差异代谢物区分度良好(Q2>0.5),44个差异代谢物均有不同程度的回调。PC (15∶0/20∶2(11Z,14Z))、PC (18∶1(9Z)/18∶1(9Z))、水杨醛和乙醇酸的表达量在血瘀证大鼠模型中下调,给予大黄可使之上调。(±)8-HETE、牛磺脱氧胆酸和γ-鼠胆酸的表达量在血瘀证大鼠模型中上调,给予大黄可使之下调。差异代谢物富集于97条代谢通路,涉及脂质代谢途径、炎症因子和免疫途径和类固醇激素合成途径等过程。本研究从血浆代谢的角度阐明了大黄治疗血瘀证的机制,为大黄的进一步开发及临床应用提供理论依据。本研究已获得陕西中医药大学实验动物伦理委员会批准(批准号:SUCMDL20210309002)。
关键词:    大黄      血瘀证      代谢组学      差异代谢物      作用机制     
Research on multivariate statistical analysis and metabolic regulation mechanism of Rhei Radix et Rhizoma treating blood stasis syndrome based on UHPLC-Q-TOF/MS
WANG Yan-xia, SHEN Xia*, YAN Yong-gang*, PENG Liang, YANG Bing-yue, PING Fan, ZHU Lin, SHE Xin-hua
Shaanxi Qinling Application Development and Engineering Center of Chinese Herbal Medicine, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China
To study the multivariate statistical analysis and metabolic regulation mechanism of rhubarb in the treatment of blood stasis syndrome through the ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). In this study, multivariate statistical analysis was used to comprehensively analyze the differential characteristics of metabolites with significant regulatory effect in plasma samples of blood stasis model rats, analyze the changes of differential metabolites of rhubarb regulating blood stasis syndrome, and analyze the pathway enrichment of identified metabolites. The results showed that the differentiation of plasma differential metabolites between the model group and the control group was good (Q2 > 0.5), and 44 differential metabolites all had different degrees of callback. The expressions of PC(15:0/20:2(11Z,14Z)), PC(18:1(9Z)/18:1(9Z)), salicylaldehyde and glycolic acid were down-regulated in the rat model of blood stasis syndrome, and rhubarb could up-regulate them. The expression levels of (±)8-HETE, taurodeoxycholic acid and γ-murocholic acid were up-regulated in the blood stasis rat model, which could be down-regulated by rhubarb. Differential metabolites are enriched in 97 metabolic pathways, involving lipid metabolism pathways, inflammatory factors and immune pathways, and steroid hormone synthesis pathways. This study clarified the mechanism of rhubarb in the treatment of blood stasis syndrome from the perspective of plasma metabolism, and provided a theoretical basis for the further development and clinical application of rhubarb. This study has been approved by the experimental animal Ethics Committee of Shaanxi University of Traditional Chinese Medicine (No. SUCMDL202103009002).
Key words:    Rhei Radix et Rhizoma    blood stasis syndrome    metabolomics    differential metabolite    mechanism of action   
收稿日期: 2021-10-09
DOI: 10.16438/j.0513-4870.2021-1460
基金项目: 国家自然科学基金资助项目(82003899,81973592);陕西中医药大学“秦药”品质评价及资源开发学科创新团队项目(2019-QN01);陕西中医药大学校级科研课题(2020GP09).
通讯作者: 沈霞,Tel:15319088980,E-mail:shenxtgyx@126.com;颜永刚,Tel:13892062171,E-mail:yunfeng828@163.com
Email: shenxtgyx@126.com;yunfeng828@163.com
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沈霞*  在本刊中的所有文章
颜永刚*  在本刊中的所有文章
彭亮  在本刊中的所有文章
杨冰月  在本刊中的所有文章
平凡  在本刊中的所有文章
朱琳  在本刊中的所有文章
佘鑫华  在本刊中的所有文章

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