体外方法研究海洋药物911和971对大鼠CYP2E1的影响

研究海洋药物911，971对大鼠CYP2E1是否有抑制或诱导作用，以及这种作用是否具有性别差异。取大鼠，雌雄各半，随机分为6个组：Ⅰ)雄性对照组、Ⅱ)雄性911组、Ⅲ)雄性971组；Ⅳ)雌性对照组、Ⅴ)雌性911组、Ⅵ)雌性971组，均采用钙离子沉淀法制备肝微粒体。在各组肝微粒体中同时给予一定剂量的探针药物及目标药物，进行孵育。于不同时间点取样，测定该探针药物的剩余浓度并计算其体外半衰期。结果表明：药物911对CYP2E1活性无影响，971对雌性大鼠CYP2E1活性无影响，但对雄性大鼠的CYP2E1有显著诱导作用。由此可得出：药物对CYP2E1的影响存有明显的性别差异，971在同各种与CYP2E1代谢有关的药物合用时，应充分考虑其在不同性别间的差异，以避免可能出现的毒性反应或不良反应。

The Effects of Ocean Drug Candidates on CYP2E1 in Vitro

The effects of ocean drug candidates on CYP2E1 in rats and their sex-based differences were studied. All rats, half male and half female, were divided into six groups randomly: I) male control group, and II) male 911 group, III)male 971 group; IV) female control group, V) female 911 group, and VI) female 971 group. All liver microsome were prepared by the calcium-ion deposition method. Both the probe drug and the drug candidates were added into different groups and incubated, the samples were selected at different times and the residual concentrations of the probe drug was determined. Furthermore, the t 1/2 s in vitro were calculated. The results showed that drug 971 had a significant inducing effect on CYP2E1 in male rats while it had no effect in female rats. Drug 911 had no effect on both male and female rats. CONCLUSION: The influence of 971 on CYP2E1 was sex-dependent. This sex-based difference should be considered carefully when 971 is used in future experiments, or administrated with other drugs related to CYP2E1 in order to avoid potential toxic or adverse effects.