黄连解毒汤对尼莫地平在大鼠脑内处置动力学的影响

Dynamic effect of Huanglian Jiedu Tang on Nimodipine disposition in rat brain

目的在整体和离体水平上研究黄连解毒汤对尼莫地平脑处置动力学的影响。方法测定大鼠单独给予尼莫地平以及尼莫地平与黄连解毒汤合用的血浆、脑组织中的尼莫地平经时过程,并在离体水平上采用原代培养的大鼠脑微血管内皮细胞(rBMEC)模型考察ig黄连解毒汤后的大鼠血清、黄连解毒汤中的指标成分黄芩苷和小檗碱对尼莫地平在血脑屏障上转运的影响。结果整体实验中,合用黄连解毒汤组,尼莫地平在血浆和脑组织中的Cmax和AUC均显著高于单独给予尼莫地平组;离体实验中,ig黄连解毒汤后的大鼠血清、黄芩苷(5μg/mL)、小檗碱(>10ng/mL)促进rBMEC对尼莫地平的摄取,小檗碱(10ng/mL)对尼莫地平的摄取没有影响。结论在合用黄连解毒汤时,尼莫地平在大鼠血浆和脑组织中的药动学行为均发生改变;合用组尼莫地平在大鼠脑组织中分布增加,可能部分源于黄连解毒汤中黄芩苷的作用。

Objective To evaluate the dynamic effect of Huanglian Jiedu Tang （HLJDT） on Nimodipine disposition in rat brain. Methods In vivo, Nimodipine in plasma and brain tissue was measured in rats treated with Nimodipine alone or Nimodipine co-administered with HLJDT. In vitro, primary cultured brain mierovessel endothelial cells （rBMEC） model was used to study the effect of serum obtained from HLJDT-treated rats, baiealin and berberine on the transport of Nimodipine across bloodbrain barrier. Results In vivo, Cmax and AUC of Nimodipine were much higher than those in Nimodipine alone group when concomitantly ig adminstered HLJDT and the concentration of Nimodipine in braine tissue also increased in HLJDT-treated rats. In vitro, the serum of HLJDT-treated rats increasd the uptake of Nimodipine in rBMEC, so did baicalin （5 μg/mL） and berberine （〉10 ng/mL）. But berberine （10 ng/mL） showed no effect on the uptake of Nimodipine. Conclusion The experimental findings indicate that HLJDT pretreatment might alter the pharmacokinetic behavior of Nimodipine both in plasma and brain tissue. The change of pharmacokinetic behavior of Nimodipine in brain tissue might partly result from the effect of baicalin in HLJDT.