糖尿病模型大鼠肝脏CYP2E1酶活性的变化

采用四氧嘧啶诱发糖尿病大鼠模型,测定肝苯胺羟化酶及其他药酶活性,同时用氯唑沙宗探针间接评价CYP2E1的活性。结果表明,糖尿病大鼠苯胺羟化酶活性增加80%,伴有其他药酶活性增加。大鼠单次po氯唑沙宗50mg·kg^-1,糖尿病组氯唑沙宗的C_max和AUC分别减少37%和34%,6 羟氯唑沙宗的Tpeak缩短,羟化指数(OH-CZX与CZX的AUC比或浓度比)升高表明糖尿病大鼠可诱导CYP2E1活性。提示糖尿病患者服用经CYP2E1酶代谢的药物应慎重。

CHANGES OF CYP2E1 ACTIVITY IN DIABETIC RAT MODEL

Diabetic rat model was induced by alloxan. To evaluate CYP2E1 activity indirectly, the activities of aniline dehydroxylase and other drug metabolic enzymes were measured. The pharmacokinetic profile of chlorzoxazone(CZX), a drug probe for CYP2E1, was obtained after a single oral dose of 50 mg.kg-1. The results indicated that diabetes increased aniline dehydroxylase activity by 53%. The Cmax and AUC of chlorzoxazone in diabetic rats were reduced 37% and 34%, respectively. The Tpeak of 6-hydroxychlorzoxazone in diabetic rats was shortened apparently. The hydroxylation index described by the AUC ratio of 6-hydroxychlorzoxazone to chlorzoxazone or the ratio of concentration of 6-hydroxychlorzoxazone to chlorzoxazone, which indicated the ability of hydroxylation, was increased in diabetes. In conclusion, diabetes can induce CYP2E1 activity, suggesting that diabetic patients should be cautious when taking some therapeutic drugs which metabolized by CYP2E1.