通脉颗粒活血通脉功效的指征药效成分研究  

Investigation on Active Components in Tong-Mai Granules Reflecting Its Effect of Activating Blood Circulation Based on Serum Pharmacochemistry/Serum Pharmacology

作　　者：张颖[1] 李丹[1] 韩笑[1] 刘春旭[1,2] 林成仁[1] 杨秀伟[2] 刘建勋[1] 

机构地区：[1]中国中医科学院西苑医院基础医学研究所/中药药理北京市重点实验室,北京100091 [2]北京大学天然药物及仿生药物国家重点实验室,北京100191

出　　处：《世界科学技术-中医药现代化》2015年第7期1398-1404,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：科技部科技重大科技专项(2009ZX09502-006):以"开心散"和"通脉颗粒"为载体的中药复方药代动力学研究关键技术(子课题);负责人:张颖;国家重点基础研究发展计划"973计划"(2015CB554405):气血相关理论的生物学基础研究;负责人:刘建勋;中国中医科学院科技创新团队项目(YS1303):中药药效学研究与评价创新团队;负责人:刘建勋

摘　　要：目的:通脉颗粒(Tongmai Granule,TM)由丹参、川芎和葛根组方而成,具有活血通脉的功效,在临床用于缺血性心脑血管疾病的治疗。本研究采用血清药化和血清药理相结合的方法,研究TM功效的物质基础。方法:大鼠单次和多次给药后采集不同时间点的血清,采用LC-MS/MS定量分析血清中TM化学成分,以心肌细胞缺氧复氧模型评价TM含药血清的心肌保护作用,并对TM入血成分与心肌细胞活力进行相关性分析。结果:8种葛根黄酮成分、5种丹参酚酸成分和2种葛根成分均能快速吸收入血,大部分成分在5或30 min达到最高浓度,反复给药3次后的血药浓度均较单次给药明显升高;含药血清具有显著的保护心肌细胞缺氧复氧损伤的作用,并具有量效关系;其中大豆苷元(TMF1)、紫草酸(LA)、丹酚酸A(SAA)、丹参素(DSS)和迷迭香酸(RA)与心肌细胞活力最相关。结论:大豆苷元(TMF1)、紫草酸(LA)、丹酚酸A(SAA)、丹参素(DSS)和迷迭香酸(RA)可能是TM活血通脉功效的指征药效成分,血清药化/血清药理关联的研究为中药复方功效物质基础提供了确证。Tong-Mai（TM） granules were composed ofRadix Salviae Miltiorrhizae（Danshen）,Rhizoma Chuanxiong（Chuanxiong） andRadix Puerariae（Gegen）. It had the effect of activating blood circulation. It had been used to treat ischemic cardio-cerebrovascular diseases in the clinical practice. This research combined serum pharmacochemistry and serum pharmaocology to study the material basis of active components in TM granules. After single or multiple intragastric administrations of TM granules, serum blood samples of rats were collected at different time points. LC-MS/MS method was developed to analyze chemical components of TM in blood serum samples. The cardiomyocyte hypoxia / reoxygenation （H/R） model was used in the evaluation of cardiomyocyte protection by TM. The correlation analysis was also conducted between serum concentration of TM and cardiomyocyte activity. The results showed that 8 components of pueraria flavonoid, 5 components of salvianolic acids and 2 components fromGegen were promptly absorbed and reached their highest concentrations at 5 or 30 min after administration. After 3 times of medication, the serum concentration was obviously higher compared to single medication. The drug-serum of TM showed significant protective effect on the cardiomyocyte H/R injury with dose-effect relationship. Daidzein, lithospermic acid, salvianolic acid A, salvianic acid A and rosmarinic acid presented as the most correlated components linked to the effect of activating blood circulation by TM. The serum pharmacochemistry / serum pharmacology related studies provided references for the verification of material basis of active components in compound Chinese medicine.

关 键 词：通脉颗粒 血清药化 血清药理 LC-MS/MS 心肌细胞缺氧复氧损伤 

分 类 号：R285.5[医药卫生—中药学]