甲磺酸加替沙星对大鼠肝微粒体细胞色素P450酶系的影响

目的研究甲磺酸加替沙星对大鼠肝微粒体细胞色素P450酶系的影响。方法将Wistar大鼠分为空白对照组、甲磺酸加替沙星高、中、低剂量组（240、160、80mg·kg^-1），ip，qd，共7d。采用差速离心法制备大鼠肝微粒体；BAC法测定蛋白浓度；分光光度法检测肝微粒体细胞色素P450酶含量及活性；单因素方差分析进行统计。结果给药组大鼠的肝重、微粒体细胞色素P450含量均明显降低，细胞色素b5的含量增高，但增高的趋势随剂量增加有所抑制；对NADPH-Cytc还原酶的影响：低、中剂量组与对照组比较有显著性差异（P〈0.01），高剂量组与对照组比较无显著性差异（P〉0.05），组间比较有显著性差异（P〈0.05）；对氨基比林-N-脱甲基酶和红霉素-N-脱甲基酶的影响：给药组与对照组比较有显著性差异（P〈0.01），组间比较也有显著性差异（P〈0.05，P〈0.01）。另外，在中、高剂量组大鼠出现肝硬度增加、腹水等现象。结论甲磺酸加替沙星对大鼠肝微粒体细胞色素P450酶具有一定的影响，对NADPH-Cytc还原酶有诱导作用，对氨基吡啉-N-脱甲基酶和红霉素-N-脱甲基酶有抑制作用。可能引起肝药酶对某些药物代谢的改变。

The Characteristics Effects of Gatifloxacin on Liver Microsome Cytochrome P450 in Rats

AimTo investigate the effects of gatifloxacin on liver microsome cytochromes P450 in rats. Methods The Wistar male rats were divided into control group（CG） and gatifloxacin groups. The rats of CG were given saline only and the rats of gatifloxacin groups were administered at 240mg·kg^-1 （high-dosage group, HG） , 160mg·kg^-1 （medial-dosage group, MG） and 80mg·kg^-1 （low-dosage group, LG） by peritoneal injection （i. p）, respectively, qd for seven days. The concentration of protein in liver microsome was determined by the BAC method. The content and activity of cytochrome P450 （ CYP450 ） was detected by spectrophotometer. Results The liver weight and content of CYP450 in rats of gatifloxacin groups were significantly lower than those in CG. The content of cytochrome b5 in rats of treatment groups was increased while the tendency was inhibited by increasing the drug＇s dosage. Compared with CG,gatifloxacin improved obviously the activity of NADPH-cytochrome C reductase（ P 〈 0.01 ） except HG（ P 〉 0.05）. Moreover, there was statistically significant difference between the three treatment groups （ P 〈 0.05）. In terms of the gatifloxacin＇s effect on erythromycin-N-demethylase and aminopyrine-N- demethylase, the significant difference was exhibited between the treatment groups and control group（ P 〈0.01 ） as well as between the three gatifloxacin groups（ P 〈0.05, P 〈0.01 ）. In addition, the hepatic toxicity of gatifloxacin was observed in MG and HG. Conclusion Gatifloxacin affected CYP450 of rats to some extent, and at the same time induced the activity of NADPH-cytochrome C reductase and inhibited that of erythromycin-N-demethylase and aminopyrine-N- demethylase,which could result in the change of metabolism of some medicine by liver drugs enzymes.