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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大鼠随机分为5组,对照组、模型组、高剂量对照组、高剂量模型组和低剂量模型组,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 PD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)晚于血液,药-时曲线下面积(AUC0-∞)和达峰浓度(ρmax)小于血液。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,血液药动学行为不能完全反映纹状体中的情况。
OBJECTIVE: To investigate the effect of levodopa (L-DOPA) on the extracellular fluid concentration in blood and striatum of Parkinson’s disease (PD) rats over time The law of change. Methods SD rats were randomly divided into 5 groups: control group, model group, high-dose control group, high-dose model group and low-dose model group. The rats were injected 6-hydroxydopamine Site microdialysis sampling. The concentrations of L-DOPA in blood and striatum were detected by HPLC-FLD and HPLC-ED respectively. Application of DAS software to fit pharmacokinetic parameters. Results After PD intraperitoneal administration, the drug rapidly absorbed into the blood and entered the striatum through the blood-brain barrier. The blood-striatal extracellular L-DOPA drug-time curve was consistent with the one-compartment model. The peak time (tmax) of L-DOPA in striatal extracellular fluid was later than that in blood and drug- ) And reached the peak concentration (ρmax) less than the blood. Conclusion There are time lags in the extracellular fluid pharmacokinetics of striatum in conscious PD model rats compared with those in blood. The concentration of blood and brain drug is dependent on the dosage of blood. The pharmacokinetics of blood can not fully reflect the Happening.