首乌方对帕金森病模型大鼠血液和纹状体细胞外液左旋多巴药代动力学影响的研究  

Synchronous Pharmacokinetics Study on Effects of Shouwu Fang on Levodopa in Blood and in Extracellular Fluids of Striatum in Rats with Parkinson's Disease

作　　者：孙晓芳[1] 王丹巧[2] 吴兆恩[2] 李鹏[2] 牛建昭[1] 王继峰[1] 王巍[3] 

机构地区：[1]北京中医药大学基础医学院,北京100029 [2]中国中医科学院医学实验中心,北京100700 [3]中国中医科学院西苑医院,北京100091

出　　处：《中国实验方剂学杂志》2011年第11期111-115,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(30772780);中国中医科学院基本科研业务费自主选题资助项目(ZZ2006037)

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,同步探讨首乌方对左旋多巴(L-DOPA)在帕金森病(PD)大鼠血液和纹状体细胞外液药动学的影响。方法:SD大鼠分为4组,对照组、模型组、左旋多巴组、首乌方+左旋多巴组。脑内注射6-羟基多巴胺(6-OHDA)造模,首乌方+左旋多巴组提前ig首乌方煎剂(生药量18 g·kg-1.d-1)6 d,各给药组单次ip L-DOPA 24 mg·kg-1和盐酸苄丝肼6 mg·kg-1。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)检测血液、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:与左旋多巴组相比,首乌方+左旋多巴组血药浓度在6个时间点升高,纹状体细胞外液药物浓度在给药后15 min时降低(P<0.05)。左旋多巴组、首乌方+左旋多巴组血液药动学参数分别为:AUC(1 627.7±420.6)mg.L-1.min-1,(2 626.4±980.6)mg.L-1.min-1;Tmax30 min,(37.5±8.2)min,MRT(0-t)(71.98±3.19)min,(83.44±9.53)min。纹状体细胞外液药动学参数分别为:Tmax(50.0±15.5)min,(81.0±27.3)min,MRT(0-t)(68.7±15.34)min,(107.9±26.7)min。与左旋多巴组相比,首乌方+左旋多巴组血液AUC增加(P<0.05),Tmax延后(P<0.05),MRT(0-t)延长(P<0.05)。纹状体细胞外液Tmax滞后(P<0.05),MRT(0-t)延长(P<0.05)。结论:首乌方可减慢L-DOPA消除,增加血液L-DOPA的吸收,减少纹状体L-DOPA药物浓度波动。Objective：To synchronously investigate the effects of Shouwu Fang on the pharmacokinetics of levodopa（L-DOPA） in blood and in extracellular fluids of striatum in rat with Parkinson＇s disease（PD）,by simultaneous blood-brain microdialysis in freely moving rats.Method：SD rats were randomly divided into four groups：control group,model group,L-DOPA group（ip L-DOPA 24 mg·kg-1and benserazide 6 mg·kg-1）,SWF＋L-DOPA group（ip L-DOPA pretreated with ig SWF）.The rat model of Parkinson＇s disease was induced by injecting 6-hydrodopamine（6-OHDA） into striatum of rats,blood-brain microdialysis technique was used for simultaneously sampling.High performance liquid chromatography-fluorescence detector（HPLC-FLD） and high performance liquid chromatography-electrochemical detector（HPLC-ED） were used to detect the concentration of L-DOPA in blood and striatum.The data were analyzed with DAS program.Result：Compared with L-DOPA group,the blood L-DOPA concentration of SWF＋L-DOPA group was increased significantly at 6 time points,the concentration in striatum was decreased at 15 min after drug administration.The blood pharmacokinetic parameters of L-DOPA group and SWF＋L-DOPA group were as follows：AUC（1 627.7±420.57） mg·L-1·min-1,（2 626.44±980.6） mg·L-1.min-1,Tmax：30 min,（37.5±8.22） min,MRT（0-t）;（71.98±3.19） min,（83.44±9.53） min,striatum pharmacokinetic parameters：Tmax：（50±15.49） min,（81±27.25） min,MRT（0-t）;（68.65±15.39） min,（107.91±26.66） min.Compared with L-DOPA group,SWF＋L-DOPA group blood AUC was increased（P0.05）,Tmaxand MRT（0-t） were delayed（P0.05）;striatum Tmaxand MRT（0-t） were delayed too（P0.05）.Conclusion：Shouwu Fang delayed L-DOPA elimination,increased its absorption in blood,and reduced fluctuation of concentration in striatum.

关 键 词：脑内微透析 血液微透析 首乌方 左旋多巴 药动学 

分 类 号：R285.5[医药卫生—中药学]