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目的 :研究中药十八反中人参与藜芦合用对P4 5 0同工酶在酶活性及mRNA水平的调控作用。方法 :采用紫外分光光度法测定大鼠肝微粒体细胞色素P4 5 0与细胞色素b5含量及氨基比林N 脱甲基酶 (APND)、对硝基苯酚羟化酶 (pNPH)活性。采用RT PCR技术检测大鼠肝中 5种P4 5 0同工酶CYP1A1,CYP2B1/ 2 ,CYP2C11,CYP2E1及CYP3A1mRNA的表达。结果 :人参与藜芦合用可明显降低P4 5 0蛋白含量 ,可降低细胞色素b5的含量 ,单药及其与藜芦配伍都能使APND活性下降。在mRNA水平上 ,藜芦可诱导CYP2C11的基因表达 ,与人参合用后却使得CYP2C11的表达下降。藜芦与人参配伍诱导了CYP1A1的表达。人参可抑制CYP2B1/ 2的基因表达 ,与藜芦合用后却明显诱导了CYP2B1/ 2的表达 ,人参与藜芦合用后也明显诱导了CYP3A1的表达。结论 :人参与藜芦配伍前后对一些CYP亚型调控作用发生明显变化 ,可能存在基于药物代谢酶机理的相反作用 ,需进一步结合代谢研究加以综合分析 ,阐明相反作用的机理
Objective : To study the regulation of P450 isoenzyme activity and mRNA level by the participation of eighteen Chinese herbs in Chinese medicine. METHODS: The contents of cytochrome P450 and cytochrome b5, aminopyrine N demethylase (APND) and p-nitrophenol hydroxylase (pNPH) were determined by UV spectrophotometry. The RT-PCR technique was used to detect the expression of five P450 isozymes CYP1A1, CYP2B1/2, CYP2C11, CYP2E1 and CYP3A1 mRNA in rat liver. RESULTS: When people participated in the combined use of Alnus cremastogyne, the content of P450 protein could be significantly reduced, and the content of cytochrome b5 could be reduced. The single-drug and its combination with Veratrum could decrease the APND activity. At the mRNA level, Veratrum can induce CYP2C11 gene expression, but combined with ginseng actually makes CYP2C11 expression decreased. Veratrum and ginseng compatibility induced the expression of CYP1A1. Ginseng can inhibit the gene expression of CYP2B1/2, but it can obviously induce the expression of CYP2B1/2 after combined with veratrum, and it can also induce the expression of CYP3A1 after the human participate in the combined use of veratrum. Conclusion: The regulation of some CYP isoforms before and after the compatibility of Veratrum repens is changed obviously, and there may be the opposite effect based on the mechanism of drug metabolism enzyme. It is necessary to further integrate the metabolism analysis to analyze the mechanism of the opposite effect.