塞络通灌胃后人参皂苷在大鼠体内的药代动力学及脑分布研究

Pharmacokinetics and brain distribution of ginsenosides after administration of Sailuotong

塞络通(SLT)是由人参、银杏叶、西红花组方,主治血管性痴呆的现代复方中药。为探讨SLT药效物质基础,并为给药方案提供依据,该文对治疗剂量SLT给与大鼠后,人参皂苷成分的血药浓度、药代特征、以及脑分布进行了研究。实验建立了同时检测生物样品中7种人参皂苷的高灵敏度LC-MS/MS分析方法,经过对线性、专属性、回收率、准确度、精密度的考察,所建立的分析方法符合临床前药代动力学研究要求。灌胃SLT 60 mg·kg-1后,7种目标成分均在大鼠血浆中检出,其中二醇型皂苷比三醇型的皂苷有更高的血药浓度和更长的消除半衰期。血浆中人参皂苷Rg1,Re,Rb1,Rb2/b3,Rc,Rd的平均消除半衰期分别为15.26,2.46,18.41,27.70,21.86,61.58 h;平均峰浓度分别为7.15,2.83,55.32,30.22,21.42,8.81μg·L-1。SLT给药后人参皂苷成分能够迅速进入脑组织,但是随时间下降很快。人参皂苷Rg1,Re,Rb1,Rc脑组织中含量较高的成分。研究结果显示服用SLT后,人参皂苷成分能够快速吸收入血并进入脑组织。人参皂苷,尤其是Rg1,Re可通过快速进入脑组织直接作用于神经细胞发挥作用;以二醇型为主的人参皂苷在血浆中长时间滞留,连续给药方式时会累计达到较高稳态血药浓度,它们可能是通过对外周的药理作用保护脑组织的主要成分。

Sailuotong （SLT） is a compound preparation composed of ginseng, ginkgo and saffron for the treatment of vascular dementia. In order to identify its material foundation and provide evidence for therapeutic regimen, the pharmacokinetics and brain dis- tribution of ginsenosides were investigated after intragastric administration of SLT. An LC-MS/MS method was developed for the deter- mination of 7 ginsenosides in rat plasma simultaneously. Statistical analysis of obtained data demonstrated that the method has achieved the desired linearity, precision, accuracy and sensitivity. After administration of SLT at 60 mg · kg^-1 dose, 7 ginsengosides were all absorbed into systematic circulation. The quantitative and statistical analysis of gensenosides in plasma showed that protopanaxdiol sap- onins exhibited higher concentration and longer half life than protopanaxatriol saponins. The mean value of half life of ginsenosides Rg1 , Re, Rbl, RbJb3, Rc and Rd were 15. 26, 2.46, 18.41, 27. 70, 21.86 and 61.58 h respectively. The peak concentration of them were 7. 15, 2. 83, 55.32, 30. 22, 21.42,8. 81 μg · L^-1 respectively. The determination of brain distribution at different time af- ter dosing revealed ginsenosides entered into brain promptly but the concentration declined along with time rapidly. The ginsenosides with higher concentration in brain were Rg~, Re, Rb~ and Rc. These findings demonstrated ginsenosides could be absorbed in blood and penetrated into brain rapidly. Some ginsenosides, especially Rg1 and Re, might be the main components directly effecting neuro- cyte in brain taking advantage of their better brain distribution. While ginsenosides of mostly protopanaxdiol saponins might protect brain mainly depending on peripheral efficacy in virtue of their long residence in blood, by which higher concentration could be reached after multiple dosing.