张翠英;章洪;董宇;任伟光;陈恒文;
ZHANG Cui-ying;ZHANG Hong;DONG Yu;REN Wei-guang;CHEN Heng-wen;Guang'anmen Hospital,China Academy of Chinese Medical Sciences;College of Pharmacy,He'nan University of Traditional Chinese Medicine;

• 1:中国中医科学院广安门医院
• 2:河南中医学院药学院

摘要(Abstract)：

通过研究丹参和川芎的药效成分丹酚酸B与阿魏酸在大鼠体内的药代动力学规律,进而探讨丹参和川芎配伍机制。将大鼠随机分为3组尾静脉推注给药:丹参纯化物组(以丹酚酸B计给药50 mg·kg~(-1))、川芎纯化物组(以阿魏酸计给药0.5mg·kg~(-1))、丹参与川芎纯化物联合用药组(以阿魏酸计给药0.5 mg·kg~(-1)+丹酚酸B计给药50 mg·kg~(-1));于不同时间点采集血样,血浆经乙酸乙酯液液萃取纯化;以氯霉素为内标,采用超高效液相色谱(UPLC)测定血浆中丹酚酸B和阿魏酸的血药浓度;利用WinNonlin 6.2软件计算动力学参数,并用SPSS 19.0统计软件进行分析。建立包括线性方程、稳定性、重复性、精密度及回收率等在内的测定大鼠血浆中阿魏酸与丹酚酸B的UPLC分析方法,所建立的样品处理和分析方法均稳定可靠;所得到的主要药代动力学参数如药时曲线下面积(AUC)、平均滞留时间(MRT)、半衰期(t_(1/2))等均有显著性差异。实验结果表明丹参和川芎配伍能显著影响药效成分在大鼠体内的药动学过程,2药配伍可以促进丹酚酸B分布更广泛、消除减缓、体内作用时间延长;能促使阿魏酸的血药浓度提高,体内清除加快。
A study was made on the pharmacokinetic regularity of effective components salvianolic acid B and ferulic acid in Salviae Miltiorrhizae Radix et Rhizoma(SMRR) and Chuanxiong Rhizoma(CR) in rats,so as to discuss the compatibility mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma.Rats were randomly divided into three groups and intravenously injected with 50 mg ·kg~(-1) salvianolic acid B for the single SMRR extracts group,0.5 mg·kg~(-1) ferulic acid for the single CR extracts group and 50 mg ·kg~(-1) salvianolic acid B + 0.5 mg·kg~(-1) ferulic acid for the SMRR and CR combination group.The blood samples were collected at different time points and purified by liquid-liquid extraction with ethyl acetate.With chloramphenicol as internal standard(IS),UPLC was adopted to determine concentrations of salvianolic acid B and ferulic acid.The pharmacokinetic parameters of salvianolic acid B and ferulic acid were calculated with WinNonlin 6.2 software and analyzed by SPSS 19.0 statistical software.The UPLC analysis method was adopted to determine salvianolic acid B and ferulic acid in rat plasma,including linear equation,stability,repeatability,precision and recovery.The established sample processing and analysis methods were stable and reliable,with significant differences in major pharmacokinetic parameters,e.g.area under the curve(AUC),mean residence time(MRT) and terminal halflife(t_(1/2)).According to the experimental results,the combined application of SMRR and CR can significandy impact the pharmacokinetic process of their effective components in rats and promote the wide distribution,shorten the action time and prolong the in vivo action time of salvianolic acid B and increase the blood drug concentration and accelerate the clearance of ferulic acid in vivo.

关键词(KeyWords)： 丹酚酸B;阿魏酸;药代动力学;配伍;丹参;川芎
salvianolic acid B;ferulic acid;pharmacokinetics;compatibility;Salviae Miltiorrhizae Radix et Rhizoma;Chuanxiong Rhizoma

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81202932);; 国家“重大新药创制”科技重大专项(2013ZX09303301)

作者(Author): 张翠英;章洪;董宇;任伟光;陈恒文;
ZHANG Cui-ying;ZHANG Hong;DONG Yu;REN Wei-guang;CHEN Heng-wen;Guang'anmen Hospital,China Academy of Chinese Medical Sciences;College of Pharmacy,He'nan University of Traditional Chinese Medicine;

Email:

DOI:

参考文献(References)：

• [1]中国药典.一部[S].2010:660.
• [2]张翠英,章洪,张盈颖,等.丹参-川芎对药不同配比对有效成分提取率的影响[J].中国医院药学杂志,2014,34(13):1066.
• [3]汪芸.丹酚酸B对心脑m管疾病药理作用的研究进展[J].现代中西医结合杂志,2010,19(35):4634.
• [4]陈衡霞,许立,许波华.丹酚酸B对心肌缺血大鼠缺血心肌血管新生的影响[J].中国实验方剂学杂志,2012,18(20):180.
• [5]刘胜敏,杨志宏,孙晓波.LC-MS/MS测定6种丹参主要有效成分及其脑靶向分布研究[J].中国中药杂志,2014,39(9):1704.
• [6]Koh P O.Ferulic acid attenuates focal cerebral ischemia-induced decreases in p70S6 kinase and S6 phosphorylation[J].Neurosci Lett,2013,555:7.(4):459.
• [7]高秀艳,宋士军,崔同,等.阿魏酸对大鼠离体胸主动脉环的舒张作用及其机制[J].郑州大学学报:医学版,2013,48(4):459.
• [8]赵文红,邓泽元,范亚苇,等.阿魏酸体外抗氧化作用研究[J].食品科学,2010,31(1):219.
• [9]汪晓燕,王香明,乇丹巧,等.川芎提取物对线虫寿命的影响及分子机制研究[J].中国中药杂志,2010,35(8):1042.
• [10]张翠英,章洪,王阶.大孔吸附树脂纯化丹酚酸B的工艺研究[J].安徽农业科学,2014,42(23):7752.
• [11]章洪,李振国,张翠英.川芎中阿魏酸类效应组分的提取纯化工艺优化研究[J].安徽农业科学,2014,42(17):5410.
• [12]黄熙,夏天,任平,等.川芎伍用丹参煎剂对川芎嗪药物动力学的影响[J].中国中西医结合杂志,1994,14(5):288.
• [13]李晓蓉,李晓莉,王丽娟,等.丹参水溶性主成分丹参素和阿魏酸合用的药动学相互作用[J].中国药理学通报,2007,23(7 J:968.
• [14]唐娜,杭太俊,叶正良,等.丹参提取物中酚酸类成分稳定性及降解动力学研究[J].时珍国医国药,2013,24(7):1631.
• [15]姚宗玲,杜守颖,陆洋,等.RP-HPLC同时测定不同来源川芎中5种有效成分的含量[J].中国中药杂志,2010,35(20):2696.