灯盏花素对CYP450代谢酶和蛋白转运体及其调控因子影响的研究

The ethnic medicine Breviscapine is used mainly for supportive treatment of heart cerebrovascular disease subsidiarily and has extensive effects on other aspects. Consequently, there are also an increasing number of combination therapies between Breviscapine and other clinical drugs. Up to date, a lot of studies on Breviscapine pharmacological actions have been done. However, there is little reports on pharmacokinetics and combination therapy from the ethnic medicine Breviscapine. Under the guidance of pharmacogenetic theory to discuss interaction between Breviscapine andrelated clinical drugs through researching the effect of Breviscapine on drug metablics enzymes and transporters, which is used modern new science technologics and methods based on previous correlative studies. In addition, it will make futher discussion of effect on nuclear receptor from the ethnic medicine Breviscapine according to have been reported researches that expression of downstream gene CYP3A4 was influenced with genetic polymorphism of PXR . On the basic of above mentioned, it will be studied influence of Breviscapine on drug metablic enzymes and transport proteins in national minority population of Yunnan province to decide the correlation between efficacy and CYP3A5, transport MDR1 gene type. The methods that are involed have not been reported at home and abroad, which will provide trains of thought for combination therapy between Breviscapine and other clinical drugs, as well as for rational use of Brebiscapine.

地方药灯盏花素一直以来被用于心脑血管疾病的辅助治疗，同时还具有其他广泛的作用，故与其他临床药物联合应用的机会也越来越多。过去的研究主要集中在该药的药效学方面，而对它的药动学和药物相互作用方面研究较少。本项目拟以遗传药理学理论为指导，在前期相关研究的基础上应用现代科学新技术，通过研究灯盏花素对药物代谢酶（CYP）和转运体活性影响来探讨灯盏花素与临床相关药物相互作用，且近年来核受体PXR在CYP及转运体蛋白的表达调控中的重要作用逐渐被认识，PXR的相关研究发现其遗传多态性能影响下游靶基因CYP3A4的表达，故还将进一步探讨灯盏花素对PXR的影响，然后通过体内实验判断其效应与CYP3A5及编码转运体基因型之间的相关性。目前国内外尚未见相关报道，故通过此研究将为灯盏花素与相关药物联合应用提供理论依据，并为合理应用灯盏花素提供新思路。

灯盏花素一直以来被用于心脑血管疾病的辅助治疗，同时还具有其他广泛的作用，故与其他临床药物联合应用的机会也越来越多。过去的研究主要集中在该药的药效学方面，而对它的药动学和药物相互作用方面研究较少。本项目拟以遗传药理学理论为指导，在前期相关研究的基础上应用现代科学新技术，通过体外实验研究灯盏花素在Chang Liver 细胞中对药物代谢酶CYP3A4和CYP3A5 mRNA和蛋白表达的影响，体内实验以咪达唑仑为探药在人体内研究灯盏花素对CYP3A5各基因型代谢活性影响来探讨灯盏花素与临床相关药物相互作用。目前国内外尚未见相关报道，通过此研究将为灯盏花素与相关药物联合应用提供理论依据，并为合理应用灯盏花素提供新思路。