血脑同步微透析研究大鼠口服银杏酮酯后内酯类成分的血脑分布

Study on blood-brain distribution of lactones in rats after oral administration of Ginkgo biloba extract by blood-brain synchronization microdialysis

目的研究大鼠口服银杏酮酯(GBE)后内酯类成分在脑部和血液中的药物质量浓度及药物分布系数(AUC脑/AUC血)。方法采用血脑同步微透析方法与高效液相色谱-质谱联用(HPLC-MS/MS)技术相结合,通过在大鼠脑部和颈静脉处同步埋置探针,收集大鼠口服GBE后不同时间段的脑部和血液微透析液,用HPLC-MS/MS对透析液中的内酯类成分进行分析,根据分析结果描绘血药浓度和脑药浓度曲线图,并分别计算各成分在脑部和血液中的药物分布系数。结果大鼠ig给予GBE混悬液(600 mg/kg)后,通过HPLC-MS/MS技术,血液微透析液中能检测到银杏内酯A、B、C和白果内酯;而脑部微透析液中只能检测到银杏内酯A、B、C,无法检测到白果内酯。各类成分在脑部和血液中的药物分布系数分别为银杏内酯A 2.911%、银杏内酯B 3.126%、银杏内酯C 0.337%。结论多点同步微透析技术可以同步检测中药中多种成分在多个效应部位的分布情况,还具有活体连续取样、节省动物、采样量小、组织损伤轻等特点,能较好地为探索多成分中药的效应物质基础提供一定的参考。

Objective To study the blood and brain drug concentration and drug distribution coefficient of lactones in rats after oral administration of Ginkgo biloba extract（GBE）. Methods Blood-brain synchronization microdialysis was used in combination with HPLC-MS/MS in this study. Probes were buried into rat brain and jugular vein to collect the blood and brain micro dialysis liquid in rats after oral GBE in different periods. The lactones in the dialysate were analyzed by HPLC-MS/MS, and the blood and brain drug concentration was depicted according to the results. Then the drug distribution coefficients of each component in blood and brain（AUCbrain/AUCblood） were calculated. Results After GBE suspension（600 mg/kg） oral gavaging in the rats, the blood samples and brain samples were obtained and detected by HPLC/MS/MS. Ginkgolides A, B, and C were detected in both blood and in brain, but bilobalide could be detected just in blood. The drug distribution coefficients in the blood and brain（AUCbrain/AUCblood） were as follows： Ginkgolide A was 2.911%, ginkgolide B was 3.126%, and ginkgolide C was 0.337%. Conclusion Simultaneous multiple microdialysis technique can be used to detect multiple components in different tissues simultaneously. It also has other characteristics, such as continuous sampling on living animals with small sample volume and little tissue damage, which can save animals. In all, simultaneous multiple microdialysis could be a good method for exploring the effect components in Chinese medicine and their distribution at effect sides.