雷诺嗪对大鼠肝微粒体蛋白质及细胞色素P450的影响

Effects of Ranolazine On liver Weight,Content of Microsomal Protein,and Cytochrome P450 of Rats

目的研究雷诺嗪对大鼠肝重、肝微粒体蛋白质及细胞色素P450含量的影响。方法将大鼠分成空白对照组和雷诺嗪组各8只,雷诺嗪组连续给予雷诺嗪为50 mg.kg-1.d-1,连续灌胃给药7 d后,测定大鼠的肝重、肝微粒体蛋白质及细胞色素P450含量,氨基比林-N-脱甲基酶、红霉素脱甲基转移酶和7-乙氧基-3-异吩噁唑酮脱烃酶的活性。结果雷诺嗪灌胃7 d后,大鼠肝重、肝微粒体蛋白含量与对照组比较差异无显著性;雷诺嗪组肝微粒体细胞色素P450含量与对照组比较明显减少(P<0.01)。雷诺嗪对大鼠肝微粒体中红霉素脱甲基酶和7-乙氧基-3-异吩噁唑酮脱烃酶的活性基本无影响,对氨基比林-N-脱甲基酶有明显的抑制作用(P<0.05)。结论雷诺嗪可能引起肝药酶对某些药物代谢的改变。

Objective To study the effects of ranolazine on liver weight, contents of microsomal protein and cytochrome P450, the activities of aminopyrine-N-demethylase, erythromycin -N-demethylase and coumarin 7-hydroxylation of rats. Methods Rats were divided into two groups. One is control group, another is dosage group. After administered with an oral dose of ranolazine 50 mg · kg - 1 once daily for 7 days, the liver microsomes of rats was distilled by different velocity centrifugation. A UV method was used to detect content of cytochrome P450 in liver microsomes, and the activities of some CYP450 of rats were studied by spectrophotometer. Results The study showed that liver weight and content of cytochrome P450 in hepatic microsomes of rats decreased significantly, differences between dose group and control group were statistically significant （ P 〈 0.01 ）. The activities of ranolazine can also significantly suppress the activity of aminopyrine-N-demethylase（P 〈 0.05 ）, but can not suppress the activity of erythromycin-N-demethylase and coumarin 7-hydroxylation significantly. Conclusion Effects of ranolazine on liver weight and cytochrome P450 of rats could result in alteration of metabolism of some drugs affected by liver drug metabolic enzyme activity.