【作者】 孙晓芳； 王丹巧； 吴兆恩； 李鹏； 牛建昭； 王继峰； 王巍；

【Author】 SUN Xiao-fang1,WANG Dan-qiao2,WU Zhao-en2,LI Peng2,WANG Wei3 (1.Beijing University of Chinese medicine,Beijing 100029,China; 2. Experimental Research Center ,China Academy of Traditional Chinese Medicine ,Beijing 100700,China; 3. Xiyuan Hospital ,China Academy of Tradiational Chinese Medicine ,Beijing 100091,China)

【机构】 北京中医药大学基础医学院； 中国中医科学院医学实验中心； 中国中医科学院西苑医院；

【摘要】 目的采用清醒自由活动大鼠血-脑双位点微透析采样的方法,同步探讨左旋多巴(L-DOPA)在帕金森病(PD)大鼠血液和纹状体细胞外液药物浓度随时间变化的规律。方法 SD大鼠,脑内注射6-羟基多巴胺(6-OHDA)造模,血-脑双位点微透析采样,分别用高效液相-荧光法(HPLC-FLD)、高效液相-电化学法(HPLC-ED)检测血、纹状体细胞外液L-DOPA浓度。应用DAS软件拟合药动学参数。结果大鼠腹腔给药后,药物迅速吸收入血,并通过血脑屏障进入纹状体。血液、纹状体细胞外液L-DOPA药-时曲线符合一室模型;纹状体细胞外液L-DOPA的达峰时间(Tmax)晚于血浆,药-时曲线下面积(AUC)和达峰浓度(Cmax)小于血浆;血药浓度和纹状体细胞外液药物浓度在高、低剂量组之间存在显著差异。结论清醒PD模型大鼠纹状体细胞外液药动学过程与血液相比存在时间滞后;血、脑药物浓度与给药剂量存在依赖关系。更多还原

【Abstract】 Aim To establish the method of simultaneous plasma-brain microdialysis in freely moving rats. To investigate the pharmacokinetics of levodopa(L-DOPA) in plasma and extracellular fluids in striatum of rats, and the effect of Parkinson’s disease(PD) rats which induced by 6-hydrodopamine (6-OHDA) on it. Methods The SD rats were divided randomly into three groups:group 1(control group with high dose), group2(model group with high dose), group3(model group with low dose), PD rats induced by injecting 6-OHDA into striatum, plasma-brain microdialysis technique were used for simultaneously sampling. High performance liquid chromatography-fluorescence detector (HPLC-FLD) and high performance liquid chromatography-electrochemical detection(HPLC-ED) were used to detect the concentration of L-DOPA in plasma and brain. Results Both the plasma and striatum concentration-time profiles of L-DOPA were described by a one compartment model. Tmax, T1/2Z, AUC, Cmax in striatum were significantly different from that in plasma. The pharmacokinetic parameters of group 1 were similar with that in group2. Between Group2 and group3, it seemed dose-dependent in both plasma and brain. Conclusion Simultaneous plasma-brain microdialysis sampling can be used in the pharmacokinetics study. There were differences on pharmacokinetics of L-DOPA between striatum and plasma. PD rats which induced by 6-OHDA has no effect on pharmacokinetics of L-DOPA .更多还原