摘要
目的:研究槲皮素、山奈酚、芦丁对大鼠细胞色素P450酶6种亚型的诱导作用。方法:槲皮素组10,50,250mg.kg-1;山奈酚组10,50,250mg.kg-1;芦丁组90mg.kg-1,雄性SD大鼠连续灌胃10d,取肝脏组织,应用液质联用,反转录-聚合酶链反应,免疫印迹杂交方法分别检测CYP450酶活性,基因表达和蛋白表达的变化。结果:槲皮素10,50,250mg.kg-1组对CYP1A2蛋白表达的诱导作用呈剂量依赖型,分别提高了31.1%,82.4%,119.3%;250mg.kg-1组使CYP1A2的基因表达提高了86.3%,CYP1A2的活性增加了44.2%,CYP2E1蛋白表达提高了54.3%,CYP2E1的活性提高36.7%。山奈酚50,250mg.kg-1组诱导CYP1A2的基因和蛋白表达,分别提高了36.2%,86.8%,110.5%,204.1%;3个剂量组使CYP1A2的活性分别提高18.3%,30.1%,53.9%。芦丁90mg.kg-1组能诱导CYP1A2的活性和基因、蛋白表达,分别提高了62.1%,90.7%,176.2%;也使CYP2C11的活性增加30.6%。结论:槲皮素、山奈酚、芦丁对大鼠多种CYP450亚型有诱导作用,提示有发生药物相互作用的可能性。
OBJECTIVE To study the inductive effect of quercetin,kaempferol and rutin on liver microsomal six cytochrome P450 enzymes in rats. METHODS Male SD rats were administered daily dose of quercetin （10,50,250mg·kg^-1 ）, kaempferoi （10,50,250mg·kg^-1） and rutin （90mg·kg^-1）,ig, for 10 consecutive days. The levels of CYP450 activity,mRNA, protein in rat liver microsome were analyzed by LC/MS/MS, RT-PCR,Western blot, respectively. RESULTS CYP1A2 protein expression was increase by 31.1%,82.4%, 119. 3 % in a dose-dependent manner with quercetin at 10,50,250mg·kg^-1, respectively. 250mg·kg^-1 quercetin also increased CYP1 A2 mRNA 86. 3 %, CYPI A2 activity 44. 2 %, CYP2E1 protein 54. 3 %, CYP2E1 activity 36. 7%. 50 and 251）mg·kg^-1 kaempferol increased CYP1 A2 mRNA and protein 36. 2%, 86. 8% and 110. 5 %, 204. 1%, respec- tively. CYPI A2 activity was also increase by 18.3% 30.1% , 53. 9 % with three dose of kaempferol. CYP1 A2 activity, mRNA and protein expression were induced by 9mg·kg^-1 rutin, increased by 62. 1%, 90. 7%, 176. 2%, respectively. Rutin also increased CYP2C11 activity 30.6%. CONCLUSION Quercetin, kaempferol and rutin can induce several CYP isoforms in rats, which means the possibility of drugdrug interactions.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2010年第9期728-731,共4页
Chinese Journal of Hospital Pharmacy
基金
广东省高等学校中药有效性与安全性重点实验室开放基金(编号:kf07007)
