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。
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 CYP 1A2. 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 CYP 1 A2 and CYP3A4 metabolism, The probability of a metabolic interaction occurring is big.
出处
《现代生物医学进展》
CAS
2014年第3期429-432,共4页
Progress in Modern Biomedicine
基金
黑龙江省教育厅面上项目资助(12511571)
