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纸质出版日期:2011
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武佰玲, 刘萍, 高月, 等. 酸枣仁、远志和桔梗水提液对大鼠肝CYP450酶活性 及mRNA表达的调控作用[J]. 中国实验方剂学杂志, 2011,17(18):235-239.
WU Bai-ling, LIU Ping, GAO Yue, et al. Modulation Effects of Water Extract from and on the Activity and mRNA Expression of Cytochrome P450 Isoenzymes in Rat Liver[J]. Chinese journal of experimental traditional medical formulae, 2011, 17(18): 235-239.
武佰玲, 刘萍, 高月, 等. 酸枣仁、远志和桔梗水提液对大鼠肝CYP450酶活性 及mRNA表达的调控作用[J]. 中国实验方剂学杂志, 2011,17(18):235-239. DOI:
WU Bai-ling, LIU Ping, GAO Yue, et al. Modulation Effects of Water Extract from and on the Activity and mRNA Expression of Cytochrome P450 Isoenzymes in Rat Liver[J]. Chinese journal of experimental traditional medical formulae, 2011, 17(18): 235-239. DOI:
目的: 研究中药酸枣仁、远志和桔梗水提液对 P450同工酶在酶活性及 mRNA水平的调控作用。 方法: 大鼠ig给予酸枣仁、远志和桔梗水提液7 d后取肝脏称重并制备肝微粒体
采用紫外分光光度法测定大鼠肝微粒体细胞色素b5(Cytb5)
P450的含量及红霉素 N -脱甲基酶(ERD)的活性
高效液相色谱法测定非那西汀 O -脱乙基酶(PHD)的活性和对硝基苯酚羟化酶( p NPH)
采用RT-PCR 技术检测大鼠肝中5种P450同工酶CYP1A1
CYP1A2
CYP2E1
CYP3A1及CYP3A2 mRNA 的表达。 结果: 与对照组比较
各给药组大鼠肝指数无显著变化;酸枣仁组显著降低Cytb5含量和ERD活性
增加 p NPH活性
远志组显著升高 p NPH
极显著降低ERD活性
桔梗组显著降低CYP450含量
并明显升高PHD和 p NPH活性;在mRNA水平上
各组的CYP1A1基因均未能检出;酸枣仁组诱导CYP2E1
CYP3A1和CYP3A2基因表达
远志组抑制CYP3A1
诱导CYP3A2的mRNA表达
桔梗组诱导CYP1A2
CYP2E1
CYP3A2的mRNA表达;酸枣仁的CYP2E1、桔梗的CYP1A2和CYP2E1 mRNA水平基本与酶活性水平相平行。 结论: 酸枣仁、远志水提液诱导CYP2E1的活性;桔梗水提液诱导CYP1A2
CYP2E1的活性
酶活性变化可能主要通过影响基因转录来实现。提示若酸枣仁和远志与经CYP2E1和CYP3A代谢的药物同用
桔梗若与经CYP1A2
CYP2E1
CYP3A代谢的药物同服
有可能会影响这些药物的临床疗效
临床用药时应慎重考虑。
Objective: To study the modulatory effect of the water extract of Ziziphus jujaba Mill.var. spinosa (Bunge) Hu ex H.F.Chou(SZR)
Polygala tenuifolia Willd.(YZ)and Platycodon grandiflorum (Jacq.)A.DC.(JG)on the activity and mRNA expression of cytochrome P450 isoenzymes in rat liver. Method: The rats were killed after the animals were administred medicines once daily for consecutive 7 days
the livers were removed rapidly and weighed
and then
liver microsomes were prepared with ultra-centrifuge method
the contents of liver microsomal cytochrome P450(CYP450)
cytochrome b5 (Cytb5) and the activities of erythromycin N -demethylase(ERD) were examined by ultraviolet spectrophotometry
the activities of phenacetin O-deethylase (PHD) and p-nitrophenol-hydroxylase (pNPH) were determined by high performance liquid chromatography (HPLC).The mRNA expression level of five CYP isoenzymes CYP1A1
CYP1A2
CYP2E1
CYP3A1 and CYP3A2 were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Result: All groups were no difference in the levels of liver index compared with the blank control. SZR obviously decreased the b5 contents and CYP3A activity of liver microsomes
markedly increased the activity of p NPH. YZ obviously increased p NPH
and significantly decreased ERD activity
JG obviously decreased the b5 contents of liver microsomes
and significantly increased the activity of PHD and p NPH. At the mRNA level.The CYP1A1 gene was not detected in these groups. SZR induced the expression of CYP2E1
CYP3A1 and CYP3A2. YZ inhibited the expression of CYP3A1
induced the expression of CYP3A2. JG induced the expression of CYP1A2
CYP2E1 and CYP3A2.The mRNA level of CYP2E1 in SZR group
and the mRNA level of CYP1A2 and CYP2E1 in JG group were largely consistent with the results of the enzyme activity. Conclusion: The water extract of SZR induced the activity of CYP2E1
the water extract of JG could induce the activity of CYP1A2 and CYP2E1. The change in enzyme activity might be attributed to the increase in mRNA level. It indicates that if drugs metabolized by CYP2E1 and CYP3A are taken simultaneously with SZR and YZ
or drugs metabolized by CYP1A2
CYP2E1 and CYP3A are taken with JG
the efficacy of the above drugs will be influenced. So
the cases should be careful considered in clinical application.
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