川芎-天麻配伍对川芎中2种成分在大鼠脑内药动学的影响

目的探讨川芎?天麻配伍对川芎中川芎嗪、阿魏酸在大鼠脑内药动学的影响。方法18只大鼠随机分成川芎组、川芎?天麻(1∶0.25)组、川芎?天麻(1∶1)组,每组6只,建立血瘀型偏头痛模型。灌胃给药后,于大鼠脑内插入微透析探针,收集不同时间点脑透析液,UPLC?MS/MS法检测川芎嗪、阿魏酸含有量,绘制血药浓度?时间曲线,计算药动学参数。结果与单味药组比较,配伍组2种成分T1/2川芎?天麻(1∶1)组阿魏酸除外]、MRT0~∞、Cmax、AUC0~∞升高(P<0.05,P<0.01);川芎?天麻(1∶0.25)组两者T1/2、MRT0~∞、AUC0~∞高于川芎?天麻(1∶1)组(P<0.05,P<0.01),川芎嗪Cmax降低(P<0.05)。结论天麻可提高川芎中川芎嗪、阿魏酸脑组织吸收程度,延长作用时间,减缓消除速率,增加蓄积,其作用强度与天麻剂量有关。

Effects of Chuanxiong Rhizoma-Gastrodiae Rhizoma compatibility on the pharmacokinetics of two constituents in Chuanxiong Rhizoma in rat brain

AIM To explore the effects of Chuanxiong Rhizoma?Gastrodiae Rhizoma compatibility on pharma?cokinetics of tetramethylpyrazine and ferulic acid in Chuanxiong Rhizoma in rat brain.METHODS Eighteen rats were randomly assigned into Chuanxiong Rhizoma group,Chuanxiong Rhizoma?Gastrodiae Rhizoma(1∶0.25)group and Chuanxiong Rhizoma?Gastrodiae Rhizoma(1∶1)group,six rats in each group,after which the models of migraine due to Blood Stasis were established.After intragastric administration,microdialysis probe was inserted into rat brain,cerebral dialysates at different time points were collected,UPLC?MS/MS was adopted in the content determination of tetramethylpyrazine and ferulic acid,blood concentration?time curve was drawn,and pharmacoki?netic parameters were calculated.RESULTS Compared with the single drug group,the compatibility groups demonstrated increased these two constituents’T1/2except for that of ferulic acid in the Chuanxiong Rhizoma?Gastrodiae Rhizoma(1∶1)group],MRT0-∞,Cmax and AUC0-∞(P<0.05,P<0.01).The T1/2,MRT0-∞and AUC0-∞of two constituents in the Chuanxiong Rhizoma?Gastrodiae Rhizoma(1∶0.25)group were higher than those in the Chuanxiong Rhizoma?Gastrodiae Rhizoma(1∶1)group(P<0.05,P<0.01),along with decreased Cmax of tetramethylpyrazine(P<0.05).CONCLUSION Gastrodiae Rhizoma can enhance the absorption degrees of tetramethylpyrazine and ferulic acid in Chuanxiong Rhizoma in brain tissue,prolong the duration of action,slow down elimination rate and increase accumulation,whose action intensity is related to Gastrodiae Rhizoma dose.