红花注射液对大鼠细胞色素P450 2D6亚型的抑制作用

Inhibition of Honghua Injection on CYP2D6 in rats

目的研究红花注射液对大鼠细胞色素P450 2D6亚型(CYP2D6)的影响。方法利用探针药物右美沙芬(DM),高效液相色谱法测定各实验组(对照组,红花注射液0.9、1.8、3.6 mL/kg组)大鼠体内尿液中与体外肝微粒体温孵系统中DM的代谢率,考察红花注射液对大鼠CYP2 D6活性的影响。结果体内实验和体外实验中,红花注射液1.8和3.6 mL/kg组DM的代谢率均明显低于对照组(P<0.05、0.01);抑制实验中,体外肝微粒体温孵系统中红花注射液组和西咪替丁组DM的代谢率明显低于空白组(P<0.05);含红花生药量为30 mg/mL时红花注射液组DM的代谢率与西咪替丁(0.6 mg/mL)时DM的代谢率相近,抑制能力相当;红花注射液的IC50为10.64 mg/mL。结论红花注射液对大鼠CYP2D6有显著的抑制作用。

Objective To investigate the effect of Honghua Injection on the activity of rat liver CYP2D6. Methods The metabolic rates of probe dextromethorphan （DM） in the blank and Honghua Injection groups （0. 9, 1.8, and 3.6 mL/kg） in vivo urine and in vitro liver microsome incubated system were determined by high performance liquid chromatography （HPLC）. The variation of the metabolic rate of DM represented the effect of Honghua Injection on the activity of rat liver CYP2D6 in vivo and in vitro. Results In vivo and in vitro, the DM metabolic rates of treated groups （1.8 and 3.6 mL/kg） are lower than that in the blank group （P〈0. 05, 0.01）; The DM metabolic rates in Honghua Injection group and Cimetidine group were significantly lower than that in the blank group in inhibitory study （P〈0. 05, respectively） ; The DM metabolic rate in Honghua Injection group （30 mg/mL） was about the same as that in Cimetidine group （0.6 mg/mL）, the inhibiting ability was similar in above-mentioned two groups ; The 50% inhibitory concentration （IC50） of Honghua Injection is 10. 64 mg/mL. Conclusion The Honghua Injection could significantly inhibit CYP2D6 in rat.