冰片对川芎注射液中洋川芎内酯Ⅰ不同脑区脑内药动学的影响

Effects of Borneol on the Pharmacokinetics of Senkyunolide Ⅰ in Different Brain Regions of Rats Administrated with Ligusticum chuanxiong Injection

目的研究冰片对川芎注射液中洋川芎内酯Ⅰ不同脑区脑内药动学的影响。方法将大鼠分为川芎组和川芎冰片配伍组。川芎组仅尾静脉注射川芎注射液1.0 g·kg^-1(生药量);川芎冰片配伍组灌胃冰片0.08 g·kg^-1,同时尾静脉注射川芎注射液1.0 g·kg^-1。在给药后不同时间点取血和皮层、海马、下丘脑、纹状体4个脑区组织。样本前处理后采用HPLC法测定洋川芎内酯Ⅰ的浓度。结果洋川芎内酯Ⅰ在血浆和4个脑组织中线性关系良好,提取回收率为97.5%~101.3%,日内、日间精密度(RSD)均小于4.77%,稳定性考察为94%~103%。与川芎组比较,川芎冰片配伍组在降低血浆洋川芎内酯ⅠAUC的同时,增加皮层和海马的AUC和Cmax、纹状体的AUC(0-∞)和下丘脑的Cmax。各脑区的相对生物利用度和药物靶向指数(DTⅠ)比较,均为皮层>海马>下丘脑>纹状体。结论冰片可增加川芎注射液中洋川芎内酯Ⅰ在皮层、海马、下丘脑、纹状体组织中的分布。

Objective To study the effects of borneol(BO)on the pharmacokinetics of senkyunolideⅠ(SI)in different brain regions of rats administrated with Ligusticum chuanxiong injection(LCI).Methods Rats were divided into LCI group and LCI+BO group.Rats in LCI group were injected with 1.0 g·kg^-1 of LCI.Rats in LCI+BO group were orally given BO(0.8 g·kg^-1)and injected with above injection.Then,their blood samples were collected at different time.Rats’brains were taken and separated into the four brain regions of cortex,hippocampus,hypothalamus,and striatum.The concentrations of SI were determined by HPLC assay.Results Excellent linear relationships of SI were obtained in the plasma and four brain regions.The recoveries of the QC sample were 97.5%-101.3%.The intra-day and inter-day RSDs were less than 4.77%.The stabilities were between 94%-103%.Compared with the LCI group,BO reduced AUC of SI in the plasma,and increased AUC and Cmaxin cortex and hippocampus.AUC(0-∞)in the striatum and Cmaxin the hypothalamus were also increased.The results of relative bioavailabilities and the drug targeting indexes of the four brain regions were cortex>hippocampus>hypothalamus>striatum.Conclusion BO improved the distribution of SI from LCI in the four brain regions.