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目的:研究中药十八反中苦参与藜芦合用对P450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P450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检测大鼠肝脏中5种P450同工酶CYP1A1,CYP2B1/2,CYP2C11,CYP2E1,CYP3A1 mRNA的表达。结果:苦参及其与藜芦合用可明显降低P450蛋白含量及b5的含量,并能使APND活性下降。在mRNA水平上,藜芦可诱导CYP2C11的基因表达,与苦参合用后却使得CYP2C11的表达下降。各单药及配伍组对CYP1A1基本无表达。苦参可诱导CYP2B1/2的基因表达,而苦参-藜芦配伍组却显示了微弱的抑制作用。苦参与藜芦合用及各单药对CYP3A1的表达有一定的抑制作用。结论:苦参与藜芦配伍前后存在对CYP及其亚型的调控作用,可能存在基于药物代谢酶机制的相反作用,需进一步结合代谢研究加以综合分析,阐明相反作用的机制。
OBJECTIVE: To study the regulation of P450 isozymes on the activity and mRNA level of CYP1A by Chinese medicine XVIII. Methods: The content of cytochrome P450 and cytochrome b5 and the activities of aminopyrine N-demethylase (APND) and p-nitrophenol hydroxylase (pNPH) in rat liver microsome were determined by UV spectrophotometry. The expressions of CYP1A1, CYP2B1 / 2, CYP2C11, CYP2E1 and CYP3A1 mRNA in liver were detected by RT-PCR. Results: Sophora flavescens and its combination with veratridine can significantly reduce the P450 protein content and b5 content, and can APND activity decreased. At the mRNA level, Veratridine can induce the gene expression of CYP2C11, but the decrease of the expression of CYP2C11 after using with Sophora flavescens. The single drug and compatibility group of CYP1A1 almost no expression. Sophora flavescens can induce gene expression of CYP2B1 / 2, while the Sophora flavescens - veratridine compatibility group but showed a weak inhibitory effect. Bitter participation in the combination of veratridine and the single drug CYP3A1 expression has a certain inhibitory effect. Conclusion: Before and after the compatibility of Tribulus Terrestris with CYP, the regulation of CYP and its subtypes may exist. There may exist the opposite effect based on the mechanism of drug metabolism enzyme.