不同剂量川芎对天麻有效成分在大鼠体内的药动学影响  

Effects of Different Doses of Chuanxiong Rhizoma on Pharmacokinetics of Active Ingredients from Gastrodiae Rhizoma in Rats

作　　者：王强[1] 沈岚[1,2] 马诗瑜[1] 赵立杰[2] 赵梦娴 冯怡[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：《中国实验方剂学杂志》2015年第2期103-109,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：上海市教育委员会科研创新重点项目(12ZZ124);上海市科委科技创新行动计划项目(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项目(20123107120009)

摘　　要：目的:探讨不同剂量川芎对天麻素(GAS)及天麻苷元(HBA)在偏头痛大鼠体内药动学的影响。方法:234只大鼠随机等分为3组,川芎-天麻配比分别为1∶3(川芎、天麻剂量分别为0.163,0.484 g·kg-1),2∶3(川芎、天麻剂量分别为0.326,0.484 g·kg-1),4∶3(川芎、天麻剂量分别为0.652,0.484 g·kg-1),于给药后不同时间点采血和脑组织。采用HPLC测定GAS和HBA含量,血浆中天麻素、天麻苷元检测流动相乙腈-0.01%磷酸水(2∶98),柱温35℃;脑组织中天麻苷元检测流动相乙腈-水(3∶97),柱温30℃。利用DAS 2.0软件计算药动学参数。结果:GAS在3组大鼠血浆中的药时曲线下面积[AUC(0-t)]分别为(1 984.41±89.91),(1 708.74±108.96),(1 862.76±82.11)mg·L-1·min,平均滞留时间[MRT(0-t)]分别为(63.62±2.04),(61.69±2.40),(75.04±4.29)min,清除率(CL)分别为(0.034 3±0.002 4),(0.039 9±0.002 3),(0.031 6±0.003 2)L·min-1·kg-1。HBA在3组大鼠的脑匀浆中AUC(0-t)分别为(72 891.70±12 075.24),(64 201.77±5 921.88),(97 046.82±11 002.49)μg·L-1·min,MRT(0-t)分别为(82.15±15.34),(68.33±11.22),(96.68±8.87)min,CL分别为(0.395 5±0.072 8),(0.450 7±0.049 2),(0.301 2±0.036 7)L·min-1·kg-1。结论:川芎-天麻(4∶3)时GAS及HBA在血、脑中生物利用度较高,滞留时间延长,消除速率减缓,这与古方中川芎-天麻药对的常用剂量相符,从药动学角度证明了古方用药的合理性和科学性。Objective：To investigate influence of different dose of Chuanxiong Rhizoma （LC） on pharmacokinetics of gastrodin （GAS） and gastrodigenin （HBA） from Gastrodiae Rhizoma （GE） in migraine model rats.Method：Rats were randomly divided into LC-GE （1 ∶ 3） group （doses of LC and GE extracts were 0.163,0.484 g·kg^-1）,LC-GE （2∶3） group （doses of LC and GE extracts were 0.326,0.484 g·kg^-1） and LC-GE （4∶ 3） group （doses of LC and GE extracts were 0.652,0.484 g·kg^-1）,plasma and brain tissue was collected at different times after drug administration.Concentrations of GAS and HBA were determined by HPLC,a mixture of acetonitrile-0.01% phosphoric acid （2∶ 98） was employed as mobile phase for determination of GAS and HBA in rats plasma with temperature of column oven was maintained at 35 ℃.While mobile phase of acetonitrile-water （3∶ 97） was used for quantification of HBA in rats brain,column temperature was heated at 30 ℃.DAS 2.0 software was used to calculate pharmacokinetic parameters.Result：Area under curve [AUC（0-t）] of GAS in rats plasma from these three groups were （1 984.41 ±89.91）,（1 708.74±108.96）,（1 862.76± 82.11） mg ·L^-1min,their mean residence time [MRT（0-t）] were （63.62 ±2.04）,（61.69 ±2.40）,（75.04 ± 4.29） min,their clearance （CL） were （0.0343±0.0024）,（0.0399±0.0023）,（0.031 6±0.0032） L·min^-1·kg^-1,respectively.AUC（0-t） of HBA in rats brain from these three groups were （72 891.70 ±12 075.24）,（64 201.77 ±5 921.88）,（97 046.82 ± 11 002.49） μg ·L-1·min,their MRT（0-t） were （82.15 ±15.34）,（68.33 ±11.22）,（96.68 ±8.87） min,their CL were （0.3955 ±0.0728）,（0.4507±0.0492）,（0.301 2 ± 0.036 7） L · min--1 kg-1,respectively.Conclusion：These findings demonstrate LC-GE （4∶3）group （equivalent to crude herbs ratio of 4∶1） can enhance bioavailability,prolong MRT and reduce elimination speed of GAS in plasma as well as HBA in brain by co

关 键 词：川芎-天麻 剂量配比 天麻素 天麻苷元 药代动力学 

分 类 号：R945[医药卫生—微生物与生化药学] R283.6[医药卫生—药剂学]