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目的:观察银杏叶提取物(GbE)和丹参酮(Tan)对大鼠细胞色素P450 (CYP)亚型和谷胱甘肽转移酶(GT) 的影响。方法:SD大鼠一日一次灌胃给药10日后,选用CYP1A1,1A2,2B1,2E1及3A特异性代谢底物,检测它们在肝和肾微粒体中的活性,还同时对肺、肝和肾组织中的GT和丙二醛(MDA)及肝组织的一氧化氮(NO)进行了观察。结果:GbE和Tan均可升高(2-9.5倍)肝中CYP1A1,1A2,和2B1的活性(P<0.01);GbE可诱导(1.6倍)CYP3A(P<0.01),高剂量时对CYP2E1也有诱导作用,但Tan对CYP3A没有作用,对CYP2E1有显著的抑制(1.9倍,P<0.01)作用;GbE还可升高(5.6-8.9倍) 肾CYP1A1和1A2(2.6倍)的活性(P<0.01),但Tan无此作用,Tan可诱导肝GT的活性(P<0.05),GbE可抑制肾GT(P<0.01),Tan对肺和肾、GbE对肝和肺中的GT无影响,此外,GbE还可显著降低肺、肾和肝组织中的MDA(P<0.01)和肝中的NO(P<0.01)。结论:GbE和Tan对CYP的调节作用将会影响与其合用药物在体内的代谢消除,进一步证明了GbE为一有效的抗氧化剂和NO抑制剂。
Objective: To observe the effects of Ginkgo biloba extract (GbE) and tanshinone (Tan) on rat cytochrome P450 (CYP) isoforms and glutathione transferase (GT). METHODS: Sprague-Dawley rats were given intragastric administration once daily for 10 days and CYP1A1, 1A2, 2B1, 2E1 and 3A were used to specifically metabolize their substrates to test their activity in liver and kidney microsomes. GT and malondialdehyde (MDA) in kidney tissue and nitric oxide (NO) in liver tissue were observed. RESULTS: Both GbE and Tan increased (2-9.5 fold) the activity of CYP1A1, 1A2, and 2B1 in the liver (P<0.01); GbE induced (1.6 times) CYP3A (P<0.01), and CYP2E1 at high doses. There was also an induction effect, but Tan had no effect on CYP3A, a significant inhibition of CYP2E1 (1.9-fold, P<0.01); GbE also increased (5.6-8.9-fold) activity of renal CYP1A1 and 1A2 (2.6-fold) (P <0.01), but Tan had no such effect, Tan induced liver GT activity (P<0.05), GbE inhibited renal GT (P<0.01), Tan had no effect on lung and kidney, GbE on liver and lung GT In addition, GbE also significantly reduced MDA (P<0.01) and liver NO (P<0.01) in lung, kidney, and liver tissues. Conclusion: The regulation effect of GbE and Tan on CYP will affect the metabolism of its combined drug in vivo, further demonstrating that GbE is a potent antioxidant and NO inhibitor.