目的:观察速效救心丸和通心络胶囊对大鼠药物代谢酶细胞色素P450(CYP450)的影响。方法:给予大鼠试验药物后制备肝及小肠微粒体,CO还原差示光谱法测定肝微粒体CYP450含量,蛋白免疫印迹法检测肝微粒体中CYP1A2、CYP2C11、CYP2E1、CYP3A和肠微粒体中CYP3A蛋白的表达量。结果:速效救心丸组和通心络胶囊组与空白对照组比较,大鼠肝脏CYP450含量无显著变化(P〉0.05);但是West-ern blotting实验对肝脏和肠道中多种CYP450酶表达量测定的结果显示,速效救心丸可诱导肝脏CYP1A2表达,但抑制肝脏CYP2C11和肠道CYP3A表达(P〈0.05);通心络胶囊可诱导大鼠肝脏CYP1A2、CYP2E1蛋白表达(P〈0.05)。结论:速效救心丸和通心络胶囊对大鼠肝脏CYP450酶总量无影响,但是,在蛋白质水平对特定亚型蛋白的表达量有影响,由此可能引发的药物相互作用不容忽视。
AIM:To investigate the influence of Quick-Acting Heart Reliever and Tongxinluo capsules on drug metablic enzyme cytochrome P450(CYP450) system in rats. METHODS: Rat liver and intestine microsome were prepared after a ten-day continuous administration of Quick-Acting Heart Reliever and Tongxinluo capsules.The content of total CYP450s in rat liver microsome was measured by UV-visible absorption spectrometry.Meanwhile,the protein expression of CYP1A2,CYP2C11,CYP2E1 and CYP3A in the liver microsome and CYP3A in the small intestine microsome was detected by western blotting assay.RESULTS:No significant difference of total CYP450 content was observed between each treatment group and control group(P0.05).Western blot analysis showed that Quick-Acting Heart Reliever induced the CYP1A2 in liver microsome,but inhibited the liver CYP2C11 and CYP3A in intestine microsome;Tongxinluo capsules induced the expression of CYP1A2 and CYP2E1 in liver microsome.CONCLUSION: Quick-Acting Heart Reliever and Tongxinluo capsules exhibit induction/inhibition on the expression of CYP450 isoforms.The results suggest that the related possible side effects of drug-drug interaction could not be neglected in the period of clinical therapy.