土家药天珠散防治血管性痴呆的有效成分与作用机制研究

Study on active ingredient and mechanism in preventing vascular dementia of Tianzhusan coming from Tujia medicine

采用双侧颈总动脉永久结扎复制慢性低灌注型血管性痴呆大鼠模型,常规饲养60 d后灌胃给予天珠散0.1 g·kg-1,给药体积0.02 m L·g-1,连续3 d,制备含药血清;采用UPLC检测天珠散入血成分并推测其结构;使用Discovery Studio3.5软件进行反向找靶,并将获得的潜在靶标基因在线提交DAVID数据库进行基因富集分析。该文共推断获得天珠散5个入血成分,鉴定其中4个成分为parishin B,parishin C,parishin,偏诺皂苷元-3-O-α-L-吡喃鼠李糖基-(1→2)-β-D-葡萄糖苷;经反向找靶,获得Fit value≥0.6的药效团模型861个,从KEGG,BIOCARTA获得经文献验证的信号通路Cytokine-cytokine receptor interaction,Apoptosis等9条,提示天珠散改善血管性痴呆的药理作用与机制可能与上述入血成分及相关信号通路有关。对于少数民族传统经验方,在药效验证的前提下,综合采用血清药物化学、计算机辅助药物设计、系统生物学等技术,将有益于民族效验方物质基础、作用机制的快速发现。

To make clear of the absorbed components of Tianzhusan （TZS） and its possible mechanism in preventing vascular de- mentia （VD） ,the rats＇ models of VD were prepared by a permanent ligation of the bilateral common carotid arteries. After 60 days,rats were administrated with TZS for 0. 1 g · kg -1, and the volume is 0. 02 mL · g -1. After 3 days, the medicated serum was prepared and detected by UPLC, and then we predicted the possible chemical structure of the absorbed components of TZS. According to the ab- sorbed components, the potential targets of TZS were found by ligand profiling of Discovery Studio 3.5. All of these target genes were submitted to DAVID on-line for gene set enrichment analysis （GSEA）. The 5 absorbed components of TZS have been predicted, and four of them have been identified as parishin B, parishin C, parishin, pennogenin-3-O-α-L-rhamnopyranosy-（ 1→2 ）-β-D-glucoside. Through reverse finding targets, we got 861 pharmacophore models and 9 pathways from KEGG, BIOCARTA after document verifica- tion. These results showed that the efficacy mechanism of TZS on VD perhaps were be related with these absorbed components and pathways. If the traditional herbs could be proved effective by efficacy tests, the serum pharmacochemistry, computer-aided drug de- sign, system biology and other technologies can be used in the next experiments, which will be beneficial to fast discovery of material basis and mechanisms of traditional medicine coming form ethnic minorities.