川芎对天麻指标成分在偏头痛大鼠体内药动学的影响  

Effects of Ligusticum chuanxiong on plasma and brain pharmacokinetics of active ingredients from Gastrodia elata in migraine rats

作　　者：王强[1] 沈岚[1,2] 梁爽[2] 马诗瑜[1] 冯怡[2] 阮克锋[2] 

机构地区：[1]上海中医药大学中药学院,上海201203 [2]上海中医药大学中药现代制剂技术教育部工程中心,上海201203

出　　处：《中成药》2015年第1期62-69,共8页Chinese Traditional Patent Medicine

基　　金：上海市教育委员会科研创新项目(重点)(12ZZ124);上海市科委科技创新行动计划(12401900402);国家教育部科学技术研究重点项目(211060);国家教育部高等学校博士学科点专项科研基金(20123107120009);上海市科委上海市自然科学基金项目(11ZR1434500)

摘　　要：目的研究川芎对天麻中天麻素及天麻苷元在偏头痛大鼠体内药动学过程的影响。方法 156只大鼠被随机分为天麻组(灌胃给予天麻提取物0.484 g/kg)和川芎-天麻组(灌胃给予川芎提取物0.652 g/kg及天麻提取物0.484g/kg),先对每组大鼠皮下注射硝酸甘油注射液复制偏头痛动物模型,30 min后给予不同药物,并于给药后不同时间点取血及脑组织,采用HPLC测定天麻素及天麻苷元在血内及脑内的浓度,以DAS 2.0计算其药动学参数。结果川芎-天麻组中天麻素和天麻苷元在血中的平均滞留时间是天麻组的1.37和1.36倍,半衰期是天麻组的1.62和1.76倍,其中天麻素的清除率为天麻组的88.14%,两组相比均有统计学差异(P<0.05或0.01);川芎-天麻组中天麻苷元在脑内的药物浓度曲线下面积是天麻组的1.26倍,平均滞留时间是天麻组的1.44倍,清除率为天麻组的77.76%,与天麻组相比有统计学差异(均P<0.01)。结论川芎与天麻配伍后可显著延长天麻素、天麻苷元在血中的滞留时间和半衰期,同时也增加天麻苷元在脑中的生物利用度及滞留时间,减缓消除速率,表明川芎与天麻配伍后可显著影响天麻指标成分的血脑药动学行为,发挥协同效应。AIM To investigate the influence of Ligusticum chuanxiong（ LC） on plasma and brain pharmacokinetics of gastrodin and p-hydroxybenzyl alcohol from Gastrodia elata（ GE） in experimental migraine model rats.METHODS One hundred and fifty-six rats were randomly divided into GE group（ with 0. 484 g / kg GE extract for enema） and LC-GE group（ with a mixture of 0. 652 g / kg LC and 0. 484 g / kg GE extract for enema）. Migraine rats induced by subcutaneous injection of nitroglycerin for 30 min were administered the test agents,and their plasma and brain tissues were collected after different time intervals. The concentrations of gastrodin and p-hydroxybenzyl alcohol were determined by HPLC. The DAS 2. 0 pharmacokinetic software（ of Chinese Pharmacology Society） was used to calculate the pharmacokinetic parameters. RESULTS The MRT（ 0-t）of gastrodin and p-hydroxybenzyl alcohol in plasma of LC-GE group were 1. 37 and 1. 36 times than that of the GE group,respectively. The t1 /2were 1. 62 and 1. 76 times,and the gastrodin clearance equaled to 88. 14% that of GE group,in which all showed significant difference（ P 〈 0. 05 or 0. 01）. Meanwhile,the AUC（ 0-t）and MRT（ 0-t）of p-hydroxybenzyl alcohol in the brain tissue of the LC-GE group was 1. 26 and 1. 44 times than that of the GE group,respectively,and its clearance was 77. 76% of GE group,displaying a significant difference（ P 〈 0. 01）. CONCLUSION Thendings demonstrate that LC can not only prolong the residence time of gastrodin and p-hydroxybenzyl alcohol in plasma to improve their bioavailability,but also lengthen the residence time and slow the elimination speed of phydroxybenzyl alcohol in the brain tissue. Thus LC can remarkably influence the pharmacokinetic characteristics of active ingredients from GE in experimental migraine rats.

关 键 词：川芎 天麻素 天麻苷元 偏头痛 药动学 

分 类 号：R255.2[医药卫生—中医内科学]