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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 investigate the effect of Shouwufang on L-DOPA in the blood and striatum of Parkinson’s disease (PD) rats by sampling the blood-brain double-site microdialysis in conscious and free-moving rats. Effect of Liquid Pharmacokinetics. Methods: SD rats were divided into 4 groups: control group, model group, levodopa group, Shouwufang + levodopa group. 6-hydroxydopamine (6-OHDA) was injected intracerebrally, and Shuguangfang + L-dopa group was pretreated with ig Shouwufang decoction (crude drug dose 18g · kg-1.d-1) for 6 days, Group single ip L-DOPA 24 mg · kg-1 and benserazide hydrochloride 6 mg · kg-1. Blood-brain double-site microdialysis sampling was used to detect the concentration of L-DOPA in blood and striatum by HPLC-FLD and HPLC-ED respectively. Application of DAS software to fit pharmacokinetic parameters. Results: Compared with levodopa group, the serum concentration of leucovorin + levodopa increased at 6 time points, and the concentration of extracellular drug in striatum decreased at 15 min (P <0.05) . The pharmacokinetic parameters of levodopa and levodopa plus levodopa were AUC (6227.7 ± 420.6) mg.L-1.min-1 and (6262.4 ± 980.6) mg.L-1, respectively. min-1; Tmax30 min, (37.5 ± 8.2) min, MRT (0-t) (71.98 ± 3.19) min, (83.44 ± 9.53) min. The parameters of extracellular pharmacokinetics of striatum were: Tmax (50.0 ± 15.5) min, (81.0 ± 27.3) min, MRT (0-t) (68.7 ± 15.34) min, (107.9 ± 26.7) min. Compared with L-dopa group, the blood AUC of Shouwufang + L-Dopa group increased (P <0.05), Tmax delayed (P <0.05) and MRT (0-t) prolonged (P <0.05). Striatal extracellular fluid Tmax lag (P <0.05), MRT (0-t) extended (P <0.05). Conclusion: Shouwu prescription can slow the elimination of L-DOPA, increase blood L-DOPA absorption and reduce the concentration of L-DOPA in striatum.