恩诺沙星对2种鲟细胞色素P450活性影响的比较研究

A Comparison Study on the Effects of Enrofloxacin on the Cytochrome P450 Enzyme Activities in Two Kinds of Sturgeons

将恩诺沙星按照0、20、40、60、80、100mg/kg浓度,对小体鲟及史氏鲟口服给药5天,停药2天后对其肝脏组织中微粒体蛋白浓度及细胞色素P450(cytochrome P450,CYPP450)酶活性进行测定。试验结果表明:2种鲟体内均含有一定量的P450酶,且史氏鲟体内微粒体蛋白浓度5.029mg/g肝重及P450酶活性0.102nmol/(mg·min)均高于小体鲟相应的4.833mg/g肝重和0.088nmol/(mg·min)。而恩诺沙星对史氏鲟及小体鲟体内的细胞色素P450酶活性均有一定抑制作用,随着给药浓度从0mg/kg到100mg/kg的增加,2种鲟体内的酶活性均逐渐降低,且史氏鲟体内P450酶活性降低幅度明显大于小体鲟,至100mg/kg给药组,两者差值仅为0.003nmol/(mg·min)。对于探讨恩诺沙星在2种鲟体内的药物代谢及其与细胞色素P450酶之间相互作用的机制提供一定的理论依据。

Oral drug delivery of Enrofloxacin was performed on the starlet （Acipenser ruthenus Linnaeus） and the Amur sturgeon （Acipenser schrencki Brandt） for 5 days according to the concentration of 0, 20, 40, 60, 80, 100 mg/kg, respectively. The enzyme activities of liver microsome cytochrome P450 were measured after drug withdrawal for 2 days. The results showed that CYP450 enzyme existed in both two sturgeons with a different degree. The protein contents of microsome and CYP450 enzyme activities were 5.029 mg/g liver weight and 0.102 nmol/（mg·min） in the Amur sturgeon respectively, which were higher than in the starlet with a data of 4.833 mg/g liver weight and 0.088 nmol/（mg·min）. Meanwhile, Enrofloxacin could inhibit the CYP450 enzyme activities in vivo. With the concentration of drug delivery from 0 mg/kg to 100 mg/kg, the CYP450 enzyme activities decreased gradually in both two sturgeons and the decreasing degree of CYP450 was larger in the Amur sturgeon than in the starlet. There was no significant difference of CYP450 between the Amur sturgeon and the starlet when the drug delivery concentration was 100 mg/kg. In conclusion, this study provides some theoretical basis for searching for drug metabolism of Enrofloxacin and the mechanism between the Enrofloxacin and the cytochrome P450 in the two kinds of sturgeons.