摘要
目的观察慢性间断性低氧对大鼠肝脏P450同工酶的影响。方法♂SD大鼠随机分为对照组和实验组,实验组分别低氧3、7、14、28d。采用酶法测定血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)活性,分光光度法测定大鼠肝微粒体红霉素N-脱甲基酶(ERD)、苯胺羟化酶(ANH)活性,半定量逆转录聚合酶链式反应(RT-PCR)检测大鼠肝脏细胞色素P4503A2、2E1的mRNA表达水平。结果慢性间断性低氧对血清ALT和AST活性无明显影响;低氧7d后,大鼠肝脏ERD和ANH活性明显升高,28d时诱导率分别为155·5%和42·2%;同时CYP3A2和CYP2E1mR-NA的表达水平,也分别增加了220·5%和102·8%。结论慢性间断性低氧能明显增加大鼠肝脏ERD(CYP3A2)和ANH(CYP2E1)活性,其机制可能与其在转录水平上提高肝脏CYP3A2和CYP2E1的基因表达水平有关。
Aim To investigate effects of intermittent hypoxia on liver microsomal cytochrome P450 isoenzyme. Methods ♂ SD rats were divided randomly into five groups： one control group, four groups treated with intermittent hypoxia for 3 days, 7 days, 14 days and 28 days respectively. Activities of serum ALT and AST were determined by enzymatic methods; liver microsomal erythromycin demethylase（ERD） and aniline hydroxylase （ANH） activities were detected by spectrophotography; levels of mRNA expression of CYP3A2 and CYP2E1 were assayed with RT-PCR. Results Activities of serum ALT and AST had no changes remarkably. However, after hypoxia 7 days, ERD and ANH activities were elevated remarkably. At the 28th day, the induction rate reached the maximum （the induction rate was 155.5% and 42. 2% respectively）. Meanwhile, levels of mRNA expression of CYP3A2 and CYP2E1 in liver were also increased. Conclusion Chronic intermittent hypoxia can increase rat liver microsomal ERD and ANH activities. The mechanism is related to up-regulation of CYP3A2 and CYP2E1 expression at the transcriptive levels.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第1期91-94,共4页
Chinese Pharmacological Bulletin
基金
湖北省卫生厅基金资助课题(No301140469)
