藏药佐太对药物代谢酶CYP2C11和CYP2D1的活性及蛋白和mRNA表达的影响

Effects of Tibetan medicine Zuotai on the activity,protein and mRNA expression of CY2C11 and CYP2D1

目的探讨佐太对药物代谢酶CYP2C11和CYP2D1活性,以及蛋白和mRNA表达的影响。方法 140只SD大鼠,雌雄各半,随机分为CYP2C11(给予探针药物苯妥英)和CYP2D1(给予探针药物右美沙芬)两大组,每大组设7个小组,为对照组、小剂量单次给药组、小剂量多次给药组、中剂量单次给药组、中剂量多次给药组、大剂量单次给药组、大剂量多次给药组,每小组10只。采用探针药物法测定大鼠给予佐太后药物代谢酶活性的变化;ELISA法测定大鼠给予佐太后药物代谢酶蛋白表达的变化;实时定量PCR法测定大鼠给予佐太后药物代谢酶mRNA表达的变化。结果与对照组比较,单次给予佐太12.0 mg·kg^(-1)后,CYP2C11的活性显著升高105.3%;单次给予佐太3.8 mg·kg^(-1)后,CYP2D1的活性显著升高193.5%;CYP2D1的蛋白表达显著升高84.3%;CYP2D1的mRNA表达显著升高76.4%,其他组无显著性变化。多次给予佐太1.2、3.8、12.0 mg·kg^(-1)后,CYP2C11的活性分别显著升高436.8%、131.6%、226.3%;CYP2C11的蛋白表达分别显著升高88.1%、38.7%、54.2%;CYP2C11的mRNA表达分别显著升高126.8%、135.2%、100.0%;CYP2D1的活性分别显著升高145.2%、71.0%、58.1%;CYP2D1的蛋白表达分别显著升高84.5%、73.7%、33.4%;CYP2D1的mRNA表达分别显著升高118.2%、67.3%、36.4%,其他组无显著性变化。结论藏药佐太对CYP2C11和CYP2D1的活性,蛋白质及mRNA表达均具有显著升高效果,显示佐太在作为合剂时可诱导肝药酶代谢加快。

Objective To investigate the effects of Tibetan medicine Zuotai on the activity,protein and mRNA expression of CYP2Cll and CYP2D1.Methods 140 SD rats are randomly divided into two groups with half maleand female ： CYP2C 11 （ treated with probe drug phenytoin） and CYP2D1 （ treated with probe drug dexamethasone）. Each group were divided into seven groups with ten rats which are control group, single low-dose administration group,multiple low-dose,single middle-dose,multiple middle-dose,single high-dose,multiple high-dose.The activity of drug metabolizing enzyme in rats was determined by probe drug method.The protein and mRNA expression of drug metabolizing enzyme in rats were determined by ELISA and real-time quantitative PCR.Results Compared with the reference, the activity of CYP2C11 was significantly increased by 105.3% after treated with 12.0 mg · kg^-1 Zuotai single administration. The activity of CYP2D1 was significantly increased by 193.5% after treated with 3.8 mg· kg^-1 Zuotai single administration.The protein and mRNA expression of CYP2D1 was drastically enhanced over 84.3% and 76.4% ,and there was no significant change in other groups.After treated with Zuotai multiple ad- ministration of 1.2,3.8,12.0 mg · kg^-1, the activity of CYP2C11 and CYP2D1 show 436.8%, 131.6% ,226.3% and 145.2%, 71.0%, 58.1% improvement, respectively.The protein and mRNA expression of CYP2C 11 were drastically enhanced over 88.1% ,38.7% ,54.2% and 126.8%, 135.2%, 100.0% ,respectively.The protein and mRNA expres- sion of CYP2D1 were drastically enhanced over 84.5%, 73.7%, 33.4% and 118.2%, 67.3%, 36.4%, respectively. There was no significant change in other groups.Conclusion Tibetan medicine Zuotai can drastically enhance the ac- tivity, protein and mRNA expression of CYP2C11 and CYP2D1, show that Zuotai as a mixture can induce accelera- ting liver enzyme metabolism .