异莲心碱对大鼠CYP3A酶活性的影响

Influence of isoliensinine on activity of CYP3A in rats

目的:探讨异莲心碱对CYP3A酶活性的影响,以了解异莲心碱与CYP3A酶底物合用药时可能产生的相互作用。方法:①建立体外肝微粒体混合酶代谢体系;②以睾酮作为底物探针,用HPLC建立检测CYP3A酶代谢活性的方法,考察体外代谢体系的最佳孵育条件;③将不同浓度异莲心碱分别与睾酮共同孵育于肝微粒体代谢体系中,测定在有或无异莲心碱存在下睾酮的减少量,以评估异莲心碱对CYP3A酶代谢的影响。结果:在肝微粒体孵育体系中,睾酮体外代谢的最佳孵育条件为底物浓度200μmol/L,代谢时间210 min。异莲心碱对CYP3A酶抑制作用较弱,IC50>1 000μmol/L。结论:异莲心碱对CYP3A酶无显著影响,可以与其底物联合用药。

Objective： To investigate the influence of isoliensinine（IL） on CYP3A enzyme activity.Methods： A mixture metabolic system of liver microsome enzymes in vitro was developed.A HPLC method to test the metabolic activity of CYP3A was established with testosterone as a probe.The activities of CYP3A enzymes were measured with different IL concentrations and incubation time with testosterone.Results： In mixture metabolic system of liver microsome enzymes,the best incubation concentration of testosterone was 200 μmol/L,the best incubation time was 210 min,in this condition the IC50 of IL for CYP3A 4inhibition was 1 000 μmol/L.Conclusion： No significant interaction between IL and CYP3A is detected,which indicates that IL might be used with CYP 3A enzyme substrates.