【摘要】 目的研究慢性间断性低氧对大鼠肝脏CYP3A2和CYP2E1的影响。方法将大鼠随机分为对照组、低氧3d组、低氧7d组、低氧14d组、低氧28d组,低氧处理结束24h后,常规腹腔注射麻醉,摘取眼球血液2ml制备血清,并测定丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)、红霉素N-脱甲基酶(ERD)、苯胺羟化酶(ANH)活性;取新鲜肝组织以制备微粒体和提取核糖核酸(RNA),并以RT-PCR进行基因片段扩增以检测大鼠肝脏细胞色素CYP3A2、CYP2E1的mRNA表达水平。结果慢性间断性低氧对血清ALT、AST活性无明显影响;低氧7d后,大鼠肝脏ERD、ANH活性明显升高,28d时诱导率分别为155.5%、42.2%;同时,CYP3A2、CYP2E1mRNA的表达水平也分别增加了220.5%、102.8%。结论慢性间断性低氧能显著增加大鼠肝脏ERD、ANH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。更多还原

【Abstract】 OBJECTIVE: To investigate the effects of episodic hypoxia(EHYP) on liver CYP3A2 and CYP2E1. METHODS: Healthy masculinity rats were divided randomly into five groups: control group, 3 -day EHYP group, 7 -day EHYP group, 14 -day EHYP group, and 28 -day EHYP group. 24 h after the management of EHYP, the rats were anesthetized by intraperitoneal injection, and the eyeball blood 2ml was drawn to prepare serum. The activities of ALT and AST in the serum were determined by enzymatic methods. The activities of liver microsomal erythromycin demethylase(ERD) and aniline hydroxylase(ANH) were detected by spectrophotography. The levels of mRNA expression of CYP3A2,CYP2E1 were assayed with RT-PCR. RESULTS: The serum activities of ALT,AST showed no remarkable change. However, after 7 days of hypoxia, ERD and ANH activities were remarkably elevated, and at 28 days induction rates reached up to155.5% and 42.2%, respectively. Meanwhile, the levels of mRNA expression of CYP3A2,CYP2E1 also increased by 220.5% and 102.8%, respectively. CONCLUSION: Chronic EHYP can remarkably increase the activities of ERD and ANH, whose mechanism is probably related to up-regulating of CYP3A2 and CYP2E1 expression at the transcriptive level.更多还原