[关键词]
[摘要]
目的 探究1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠以三七总皂苷干预后,脑微透析液中三七皂苷R1(R1)、人参皂苷Rg1(Rg1)和氨基酸神经递质的含量变化。方法 给小鼠ip MPTP造成PD小鼠模型,经iv三七总皂苷(PNS)溶液后,采用微透析技术采集脑微透析液。将样品分为2部分,一部分采用UPLC-MS/MS对R1和Rg1进行药动学研究,另一部分采用氨基酸柱前衍生化和HPLC-FLD进行药效学研究。结果 小鼠iv PNS后,脑微透析液中R1的峰浓度(Cmax)为(35.48±24.4)ng/mL,Rg1的Cmax为(75.61±41.35)ng/mL。R1和Rg1的达峰时间(tmax)均为1.75 h。R1和Rg1的药时曲线下面积(AUC)分别为(100.12±84.29)ng∙h/mL和(218.84±144.73)ng∙h/mL。且给予PNS后的PD模型小鼠体内天冬氨酸和谷氨酸浓度降低,甘氨酸、牛磺酸和γ-氨基丁酸浓度增加。结论 PNS能一定程度透过血脑屏障(BBB)进入脑内,调节PD模型小鼠体内氨基酸水平的失衡,进而发挥神经保护作用。
[Key word]
[Abstract]
Objective To investigate the changes in the content of notoginsenoside R1 (R1), ginsenoside Rg1(Rg1) and amino acid neurotransmitters in brain micro dialysate after the treatment with Panax notoginseng saponins (PNS) solution in Parkinson's disease (PD) model mice induced by 1-methylmethyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods Mice were injected intraperitoneally with MPTP to induce PD mice model. After intravenous injection of PNS solution, brain micro dialysate was collected by microdialysis technique. The sample was divided into two parts, one was subjected to pharmacokinetic study of R1 and Rg1 by UPLC-MS/MS, and the other part for pharmacodynamics study which was done by pre-column derivatization of the amino acids and HPLC-FLD analysis. Results After iv administration of PNS to the mice, the maximum CSF concentration was (35.48 ±24.4) ng/mL for R1 and (75.61 ±41.35) ng/mL for Rg1. The time to reach maximum concentration was found 1.75 h both for R1 and Rg1. The AUC value of R1 and Rg1 were (100.12 ±84.29) ng·h/mL and (218.84 ±144.73) ng·h/mL, respectively. Moreover, the levels of aspartic acid and glutamic acid were reduced, and glycine, taurine and γ-aminobutyric acid levels were increased in PD model mice treated with PNS in comparison with model group. Conclusion PNS can enter the brain through the blood brain barrier (BBB) to some extent, and regulate the imbalance of amino acid level in PD model mice, so as to display the neuroprotective effect and its therapeutic value.
[中图分类号]
[基金项目]
天津市自然科学基金项目(16ZXHLGX00170)