1.8%AVM乳油对小鼠肝微粒体CYP450酶系与GST影响的初探

The preliminary investigation of the effects of 1.8%AVM latex on liver microsome cytochrome P450 and GST in mice

目的观察1.8%阿维菌素(AVM)乳油对小鼠肝微粒体细胞色素P450(CYP450)酶系与谷胱甘肽S-转移酶(GST)的影响,初步探讨1.8%AVM在肝脏的可能的代谢过程和毒性机理。方法 40只清洁级昆明种小鼠(雌雄各半)灌胃给予1.8%AVM乳油(70、35、17.5mg/kg),连续7d,以0.9%氯化钠溶液作对照。末次给药后处死小鼠,采用差速离心法制备大鼠肝微粒体,Brandford法测定微粒体蛋白浓度,CO还原差示光谱法检测肝微粒体CYP450含量,差示光谱法则定肝微粒体b5(Cyt-b5)含量,紫外分光光度法则定肝微粒红霉素N-脱甲基酶活性(ERD)和氨基比林-N-脱甲基酶(ADM)和GST的活性。结果各1.8%AVM乳油染毒剂量组ERD、ADM活性均低于对照组,差异有统计学意义(P<0.05);各剂量组小鼠肝脏指数、CYP450与b5的含量及GST的活性与对照组比较差异均无统计学意义(P>0.05),且不同剂量组间差异亦无统计学意义(P>0.05)。结论 1.8%AVM乳油可抑制小鼠肝微粒体ERD(主要反映CYP3A活性)和ADM(主要反映CYP2E1)的活力,而对CYP450和b5含量及GST活性影响小,未观察到1.8%AVM乳油对小鼠肝微粒体重要的Ⅰ相酶CYP450和Ⅱ相酶GST的诱导或抑制作用。

Objective To investigate the effect of 1.8%AVM latex on the contents and activities of cytochrome P450 （CYP450） system and glutachione S-transferase （GST） in mouse liver. Methods The Kunming mice were divided into control group （CG）and AVM groups.The mice of CG were administered with saline only and the mice of 1.8%AVM groups were administered with 70 mg/kg （high-dosage group, HG）, 35 mg/kg （medial-dosage group, MG） and 17.5 mg/kg （low- dosage group, LG） of latex by oral gavages for seven days.The differential centrifugation was used to prepare liver microsome of mice. The concentration of protein in liver microsome was determined by the Bradford method. The content of CYP450 was detected by Carbon monoxide difference spectrophotometer .The activity of ERD, ADM and GST were measured by UV spectrophotometry. Results The activity of ERD and ADM of HG, MG and LG groups were significantly reduced compared with those in CG（0.32-0.05） nmol/（min-mg） （P〈0.05）. The liver weight/10 g body weight, the content of CYP450! b5 and the activity of GST in mice of the treatment groups were not significantly different compared with those in CG （P〉0.05）. Conclusion The activity of CYP3A and CYP2E1 in mice treated with the 1.8% AVM could be inhibited. The obvious affection was not observed in AVM groups on liver microsome cytochrome P450/b5 and GST.