川芎和黄芪有效部位组合给药后川芎嗪在脑缺血再灌注大鼠体内的PK-PD结合研究  

Study on PK-PD combination of ligustrazine in cerebral ischemia reperfusion rats after ig administration of effective parts in compatibility of Chuanxiong Rhizoma and Astragali Radix

作　　者：周惠芬[1] 何昱[1] 张宇燕[1] 杨洁红 舒明春[1] 万海同[1] 

机构地区：[1]浙江中医药大学,浙江杭州310053

出　　处：《中草药》2016年第19期3463-3468,共6页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81630105;81274176;81374053);浙江省自然科学基金资助项目(LR16H270001)

摘　　要：目的探讨黄芪川芎有效部位配伍给药后川芎嗪在脑缺血再灌注大鼠体内的药动学-药效学(PK-PD)结合模型。方法建立大鼠大脑中动脉局灶性栓塞(MCAO)模型,再灌注同时ig给予黄芪川芎有效部位配伍组方(黄芪总皂苷、黄芪总黄酮、川芎总生物碱、川芎总有机酸各100 mg/kg),给药后0.083、0.25、0.5、0.75、1.0、1.5、2.0、3.0、4.0、6.0 h各时间点眼眶静脉丛取血0.5 m L。RP-HPLC测定血浆中川芎嗪的浓度,试剂盒测定大鼠血浆中乳酸脱氢酶(LDH)的活性。采用DAS 3.2.6软件拟合PK-PD结合模型,并计算药动学与药效学参数。结果大鼠血浆中LDH活性效应值与川芎嗪血药浓度不直接相关,效应滞后于血药浓度,以效应室联结的Emax模型较优。结论成功建立了黄芪川芎有效部位配伍给药后川芎嗪在脑缺血再灌注大鼠体内的PK-PD结合模型,可推广应用于预测其他中药配伍后主要有效成分的PK-PD研究。Objective To research the pharmacokinetic-pharmacodynamic （PK-PD） model of ligustrazine in cerebral ischemia reperfusion （I/R） rats. Methods To build the middle cerebral artery embolization （MCAO） model. The blood 0.5 mL was collected from orbital venous plexus at 0.083, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, and 6.0 h time points after ig administration of effective parts in compatibility prescription of Chuanxiong Rhizoma and Astragali Radix. The concentration of ligustrazine in serum was determined by RP-HPLC, and then the concentration-time curves were drawn. Meanwhile, the activities of LDH in serum were determined with ELISA Kit. PK-PD modeling was fitted with DAS 3.2.6 software. The PK-PD model parameters were calculated. Results The effect of ligustrazine on inducing LDH release did not relate directly with the concentration but lagged behind the concentration ofligustrazine in serum. The relationship between effect and serum concentration fits Emax model. Conclusion This study successfully establishes the combined PK-PD model of ligustrazine aRer ig administration of different combinations of the active parts in Chinese matefia mcdica （CMM） to rats. This research can be effectively applied to predict PK- PD studies on the main effective components in other compatibility of CMM.

关 键 词：川芎 黄芪 川芎嗪 PK-PD 大脑中动脉局灶性栓塞 脑缺血再灌注 

分 类 号：R285.5[医药卫生—中药学]