参麦注射液和注射用血塞通对大鼠肝脏及肠道药物代谢酶CYP450的影响

目的考察参麦注射液和注射用血塞通对大鼠药物代谢酶细胞色素P450(CYP450)的影响。方法连续给予大鼠试验药物后,制备肝及小肠微粒体;用CO还原差示光谱法,测定肝微粒体CYP450含量;用蛋白免疫印迹法,检测肝微粒体中CYP1A2、CYP2C11、CYP2E1、CYP3A和肠微粒体中CYP3A蛋白的表达量。结果参麦注射液和注射用血塞通组与空白对照组大鼠的肝脏总P450含量无显著性差异(P>0.05)。但参麦注射液可显著诱导肝脏CYP2E1表达,但抑制肠微粒体中CYP3A表达;肝CYP1A2、CYP2C11水平均有所上升。血塞通可显著诱导大鼠肝脏CYP1A2、CYP2E1、CYP2C11、CYP3A蛋白表达,肠CYP3A的表达水平显示出下降趋势。结论参麦注射液和注射用血塞通对大鼠肝脏P450酶总量无影响;但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。

Impact of Shenmai injection and Xuesaitong injection on CYP450s in rat liver and intestine after successive administration

Objective To investigate the influence of Shenmai injection(SM) and Xuesaitong injection(XST) on drug metablic enzyme of cytochrome P450(CYP450) system in rat.Methods Microsome of rat liver and intestine was prepared after intravenous injection of SM and XST for 10 days.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 were detected by western blotting analysis.Results Although no significant difference of total P450 content was observed between each treatment group and control group(P>0.05),but obvious difference was exhibited in western bloting analysis on CYPs.In addition to both SM and XST induced the CYP2E1 in liver microsome significantly,SM inhibited the CYP3A in intestine microsome while XST induced the expression of CYP1A2,CYP2C11 and CYP3A in liver microsome significantly.Conclusion Since the expression of CYPs subtypes in liver and intestine was significantly changed after successive administration,the possible side effect of drug-drug interaction could not be neglected in the period of clinical therapy.