尼扎替丁对大鼠CYP1A2亚型的影响

目的通过尼扎替丁的大鼠体内、外实验,观察尼扎替丁对大鼠CYP1A2亚型的影响。方法通过HPLC法测定全血中咖啡因的代谢率,观测尼扎替丁对大鼠CYP1A2活性的影响;通过W estern b lot法测定尼扎替丁对大鼠肝微粒体CYP1A2蛋白表达的调控;通过HPLC法测定肝微粒体重组系统对乙酰氨基酚的含量,确定尼扎替丁对大鼠肝微粒体CYP1A2亚型的作用。结果实验组中给予大鼠不同浓度的尼扎替丁(14、27、54 mg.kg-1),其咖啡因代谢率为29.6%±12.5%、32.4%±13.4%、37.5%±15.0%,对照组为26.9%±11.9%,各剂量组及对照组间差异均无显著性(P>0.05);实验各剂量组与对照组的CYP1A2蛋白表达差异无显著性;肝微粒体体外重组系统中,实验组各浓度尼扎替丁对CYP1A2没有抑制作用,CYP1A2的活性>100%;对照组α-萘黄酮有明显的抑制作用,IC50=0.0306μmol.L-1。结论体内、外实验结果均表明尼扎替丁对大鼠CYP1A2没有抑制作用。

Effect of nizatidine on rat CYP1A2 expression and activity

Aim The present study investigates the influence of nizatidine on rat liver CYP1A2 activity in vivo and in vitro,respectively.Methods We employed HPLC to measure the metabolites of caffeine in the blood and calculated the ratio between the metabolites and caffeine,which was used to evaluate the effect of nizatidine on rat CYP1A2 activity in vivo;We also detected the CYP1A2 activity in microsomal reconstituted system by analysis of paracetamol with HPLC.Finally,we examined the expression of CYP1A2 from microsomes treated with nizatidine or control groups using Western blot.Results The metabolism of caffeine in treated groups was 29.6%±12.5%、32.4%±13.4%、37.5%±15.0%,with different concentration of nizatidine(14,27,54 mg·kg~(-1))compared with 26.9%±11.9% in the control group,which was no significant difference among the groups(P>0.05).The expression of CYP1A2 in liver microsomes from nizatidine treated was almost similar to control groups.In rat liver microsomal reconstituted system,nizatidine has no inhibitory effect on CYP1A2 activity compared with α-naphthoflavone that significantly inhibited phenacetin O-deethylation(IC_(50)=0.0306 μmol·L~(-1)).Conclusion Nizatidine has no inhibitory effect on rat CYP1A2 in vivo and in vitro.