| 王艳 刘明远 杨光远 王立波 李娟 高伟勤 董天崴.氯吡格雷对大鼠肝药物酶CYP3A4 和CYP1A2 表达的影响[J].,2014,14(3):429-432 |
| 氯吡格雷对大鼠肝药物酶CYP3A4 和CYP1A2 表达的影响 |
| Effects of Clopidogrel on Cytochrome Oxidase Enzyme CYP3A4and CYP1A2 of Rat Liver |
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| DOI： |
| 中文关键词: 氯吡格雷 CYP3A4 CYP1A2 抑制 |
| 英文关键词: Clopidogrel CYP3A4 CYP1A2 Inhibition |
| 基金项目:黑龙江省教育厅面上项目资助(12511571) |
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| 中文摘要: |
| 目的：氯吡格雷主要由CYP3A4 催化使其激活，CYP1A2 也参与氯吡格雷活化。关于氯吡格雷对肝微粒体酶的影响国内外
文献报道不多，因此本实验通过检测肝细胞色素氧化酶CYP3A4 和CYP1A2 的表达，探讨氯吡格雷对大鼠肝药物酶的影
响。方法：生理盐水为对照组，氯吡格雷设高、中、低三个剂量组（27，13.5，6.75mg/kg/d），雄性健康大鼠连续灌胃给药7天，脱臼处
死，取肝组织，通过western blot法检测大鼠肝脏CYP3A4 和CYP1A2 蛋白表达情况。结果：1）、氯吡格雷抑制大鼠CYP3A4 蛋白
表达，氯吡格雷高中低剂量组分别比生理盐水组大鼠CYP3A4 蛋白表达量降低（P<0.05）；氯吡格雷低中高剂量组间进行比较，大
鼠CYP3A4 蛋白表达量呈梯度减少（P<0.05）；2）、氯吡格雷抑制大鼠CYP1A2 蛋白表达，氯吡格雷高中低剂量组分别比生理盐水
组大鼠CYP1A2 蛋白表达量降低（P<0.05），氯吡格雷低中高剂量组间进行比较，大鼠CYP1A2 蛋白表达量呈梯度减少（P<0.05）。
结论：氯吡格雷使肝细胞色素氧化酶CYP3A4 和CYP1A2 的表达量减少，因此氯吡格雷高、中、低3 个剂量组均不同程度的抑制
大鼠肝脏CYP3A4 和CYP1A2 的表达，提示当氯吡格雷与某些主要经CYP3A4 和CYP1A2 代谢的药物合用时，发生代谢性相关
作用的可能性大。 |
| 英文摘要: |
| Objective:Clopidogrel is metabolically activated by CYP3A4 including CYP1A2, the effects of clopidogrel on
cytochrome p450 enzymes of rat liver was investigated by detecting the expression of cytochrome oxidase enzyme CYP3A4 and
CYP1A2.Methods:30 male rats were randomly divided into 5 groups. taking normal sodium as control group, 3 groups rats were given
27, 13.5, 6.75 mg/kg/d clopidogre for 7 days respectively, to detect the expression of CYP3A4 and CYP1A2 by Western blot.Results:1.
Clopidogrel inhibited the expression of CYP3A4. Compared with normal saline group, expression of CYP3A4 were decreased in 5
group.（P<0.05）; Among the three groups, expression of CYP3A4 were gradiently decreased（P<0.05 ）. 2. Clopidogrel inhibited the
expression of CYP1A2. Compared with normal saline group, expression of CYP1A2 were decreased in 5 group.（P<0.05）; Among the
three groups, expression of CYP3A4 were gradiently decreased（P<0.05）.Conclusion:Clopidogrel made expression of CYP3A4 decrease,
so clopidogrel inhibited the expression of CYP3A4 and CYP1A2 in three group. when clopidogrel be used in combination with drug via
CYP1A2 and CYP3A4 metabolism, The probability of a metabolic interaction occurring is big. |
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