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纸质出版日期:2011
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孙晓芳, 王丹巧, 吴兆恩, 等. 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[J]. 中国实验方剂学杂志, 2011,17(11):111-115.
SUN Xiao-fang, WANG Dan-qiao, WU Zhao-en, et al. Synchronous Pharmacokinetics Study on Effects of Shouwu Fang on Levodopa in Blood and in Extracellular Fluids of Striatum in Rats with Parkinson’s Disease[J]. Chinese journal of experimental traditional medical formulae, 2011, 17(11): 111-115.
孙晓芳, 王丹巧, 吴兆恩, 等. 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[J]. 中国实验方剂学杂志, 2011,17(11):111-115. DOI:
SUN Xiao-fang, WANG Dan-qiao, WU Zhao-en, et al. Synchronous Pharmacokinetics Study on Effects of Shouwu Fang on Levodopa in Blood and in Extracellular Fluids of Striatum in Rats with Parkinson’s Disease[J]. Chinese journal of experimental traditional medical formulae, 2011, 17(11): 111-115. DOI:
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 (P<0.05)
Tmaxand MRT(0-t) were delayed (P<0.05);striatum Tmaxand MRT(0-t) were delayed too (P<0.05). Conclusion: Shouwu Fang delayed L-DOPA elimination
increased its absorption in blood
and reduced fluctuation of concentration in striatum.
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