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

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 comparing with other compatibility groups,which is consistent with usual dose in ancient prescriptions.This study demonstrates compatibility connotation at a right dose-ratio of LC and GE through angle of pharmacokinetics.