药学学报, 2022, 57(4): 1115-1122
引用本文:
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.

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
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
摘要:
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
Abstract:
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
相关功能
PDF(5218KB) Free
打印本文
0
作者相关文章
王艳霞  在本刊中的所有文章
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

参考文献:
[1] Wang ZY, Li L, Liu JX, et al. Research progress of change of platelet in blood stasis syndrome and effect of traditional Chinese medicine[J]. China J Chin Mater Med (中国中药杂志), 2021, 46:5201-5209.
[2] Vilchinsky V, Ginzburg K, Fait K, et al. Cardiac-disease-induced PTSD (CDI-PTSD):a systematic review[J]. Clin Psychol Rev, 2017, 55:92-106.
[3] Pan XL, Hao EW, Xie JL, et al. Molecular mechanism of blood-activating and stasis- removing Chinese medicine in regulating blood stasis syndrome[J]. Chin J Exp Tradit Med Form (中国实验方剂学杂志), 2018, 24:227-234.
[4] Yang YZ, Deng Y, Yang XJ, et al. Effects of different compatibility of angelica sinensis on hemorheology, coagulation function and pathology of heart and lung in acute blood stasis rats[J]. Pharmacol Clin Chin Mater Clin Med (中药药理与临床), 2018, 34:125-129.
[5] Zhang Q, Li YL. Discussion on the application of activating blood and resolving stasis in heart diseases[J]. J Liaoning Univ Tradit Chin Med (辽宁中医药大学学报), 2020, 22:111-115.
[6] Lu L, Li HQ, Fu DL, et al. Rhubarb root and rhizome-based Chinese herbal prescriptions for acute ischemic stroke:a systematic review and meta-analysis[J]. Complement Ther Med, 2014, 22:1060-1070.
[7] Li H, Hei XB, Li YM, et al. Characterization of accumulation profile of 10 constituents in various parts of Rheum officinale at different years old stage[J]. Chin Tradit Herb Drugs (中草药), 2019, 50:1690-1697.
[8] Wang HY, Yan YG, Wang YL, et al. Ancient literature data mining on the best ratio of Taoren-Dahuang to promoting blood circulation and removing blood stasis and its effects analysis on rat model of cold congelation and blood stasis[J]. Chin J Tradit Chin Med Pharm (中华中医药杂志), 2018, 33:2563-2567.
[9] Liu J, Wu F, Chen C. Design and synthesis of aloe-emodin derivatives as potent anti-tyrosinase, antibacterial and anti-inflammatory agents[J]. Bioorg Med Chem Lett, 2015, 25:5142-5146.
[10] Tan P, Zhang HZ, Li Y, et al. Preliminary study on antiplatelet aggregation of 10 anthraquinones in Rhei Radix et Rhizoma based on bioassay[J]. Chin Tradit Herb Drugs (中草药), 2018, 49:859-865.
[11] Zhang HZ, Tan P, Liu ZD, et al. Activating blood biological potency assay and chemical fingerprint chromatogram applied to quality evaluation of rhubarb[J]. Acta Pharm Sin (药学学报), 2017, 52:436-442.
[12] Nam M, Kim MS, Hwang G. Optimization and validation of capillary electrophoresis- and gas chromatography-tandem mass spectrometry methods for the analysis of intermediate metabolites in glycolysis and pentose phosphate pathways within biological samples[J]. J Chromatogr A, 2021, 1656:462-531.
[13] Sheng N, Wang CH, Jia ZX, et al. The mechanism of Er-xian decoction in regulating lipid metabolism disorders on bilateral ovariectomized rats based on metabolomics study[J]. Acta Pharm Sin (药学学报), 2021, 56:2403-2409.
[14] Gao Y, Wang P, Xu T, et al. Comprehensive analysis of antidepressant metabolic characteristics of Xiaoyao San and its mechanism of regulating energy metabolism and neurotransmitter[J]. Chin Tradit Herb Drugs (中草药), 2021, 52:1360-1368.
[15] Xu PB, Ding LD, Chou JW, et al. Study on effect of "trichosanthis fructus-allii macrostemonis bulbus" on atherosclerosis in ApoE-/- mice based on liver metabonomics[J]. China J Chin Mater Med (中国中药杂志), 2021, 46:5320-5329.
[16] Li SJ, Li WX, Tang YP, et al. Comparative analysis of the promoting blood effects of the combination of different proportions of Danggui and Honghua by the principal component analysis and multi-attribute comprehensive index methods[J]. Acta Pharm Sin (药学学报), 2014, 49:1304-1309.
[17] Tan J, Wang C, Zhu H, et al. Comprehensive metabolomics analysis of Xueshuan Xinmaining tablet in blood stasis model rats using UPLC-Q/TOF-MS[J]. Molecules, 2018, 23:1650.
[18] Yuan ZW, Zhong LJ, Ji P, et al. Plasma metabolomics of angelica intervene in blood stasis syndrome rats[J]. Nat Prod Res Dev (天然产物研究与开发), 2018, 30:559-567.
[19] Cao D, Xu C, Xue Y, et al. The therapeutic effect of Ilex pubescens extract on blood stasis model rats according to serum metabolomics[J]. J Ethnopharmacol, 2018, 227:18-28.
[20] Stamenkovic A, O'hara kimberley A, Nelson DC, et al. Oxidized phosphatidylcholines trigger ferroptosis in cardiomyocytes during ischemia-reperfusion injury[J]. Am J Physiol Heart Circ Physiol, 2021, 320:H1170-H1184.
[21] Li L, Yao DN, Lu Y, et al. Metabonomics study on serum characteristic metabolites of psoriasis vulgaris patients with blood-stasis syndrome[J]. Front Pharmacol, 2020, 11:558731.
[22] Ma CY, Liu JH, Liu JX, et al. Relationship between two blood stasis syndromes and inflammatory factors in patients with acute coronary syndrome[J]. Chin J Integr Med, 2017, 23:845-849.
[23] Sandre P, Da SC, De VP, et al. Chronic nutritional restriction of omega-3 fatty acids induces a pro-inflammatory profile during the development of the rat visual system[J]. Brain Res Bull, 2021, 174:366-378.
[24] Edwards JM, Mccarthy CG, Wenceslau CF. The obligatory role of the acetylcholine-induced endothelium-dependent contraction in hypertension:can arachidonic acid resolve this inflammation?[J]. Curr Pharm Des, 2020, 26:3723-3732.
[25] Shao J, Wang HX, Yuan GL, et al. Involvement of the arachidonic acid cytochrome P450 epoxygenase pathway in the proliferation and invasion of human multiple myeloma cells[J]. Peer J, 2016, 4:e1925.
[26] Zhao FR, Zhao LH, Wang TF, et al. ACTH and GC levels in patients with hepatitis cirrhosis at two stages and their correlation with TCM pattern elements[J]. J Beijing Univ Tradit Chin Med, 2015, 38:351-355.
[27] Huang LQ, Zhao CQ. Research progress of glucocorticoid in obstetrics and gynecology[J]. J China Pharm (中国药房), 2012, 23:4214-4216.
[28] He Y, Wang LJ, Liu TT, et al. Analysis of therapeutic mechanism of siwutang in primary dysmenorrhea syndrome based on metabolomics technique[J]. Chin J Exp Tradit Med Form (中国实验方剂学杂志), 2017, 23:82-89.
相关文献:
1.王新红, 张迟, 周丽, 曾金祥, 任玲玲, 毛竹, 袁恩, 周立分.基于代谢组学的桔梗总皂苷镇咳祛痰作用机制研究[J]. 药学学报, 2022,57(3): 757-765
2.钮敏洁, 王梦晴, 于慧, 刘鑫, 蔡皓, 曹岗, 段煜, 裴科, 张专.基于血浆代谢组学的山茱萸酒制后抗大鼠肝纤维化作用增强机制研究[J]. 药学学报, 2021,56(9): 2410-2418
3.郝海梅, 贾小叶, 周红兵, 白万富, 常虹, 石松利.基于代谢组学的蒙古扁桃药材抗大鼠肾纤维化作用机制研究[J]. 药学学报, 2020,55(9): 2182-2190
4.段亚辉, 秦雪梅, 李震宇.款冬花总倍半萜对OVA致敏哮喘大鼠干预作用的代谢组学[J]. 药学学报, 2020,55(10): 2414-2420
5.李天琪, 孙珊珊, 张金月, 王映红.高脂血症金黄地鼠粪便和肠道内容物代谢轮廓的研究[J]. 药学学报, 2018,53(5): 791-796
6.涂灿, 何琴, 周元园, 王肖辉, 张乐, 卫璐戈, 牛明, 逄瑜, 肖小河, 王伽伯.基于代谢组学的大黄对正常和肝纤维化大鼠双向作用对比研究[J]. 药学学报, 2018,53(7): 1139-1147
7.季涛, 张丽丽, 黄晓晨, 宿树兰, 欧阳臻, 朱振华, 郭盛, 尚尔鑫, 钱大玮, 段金廒.基于代谢组学的桑叶多组分治疗糖尿病的作用机制研究[J]. 药学学报, 2015,50(7): 830-835