急进高原对大鼠肝功能及CYP1A2、CYP3A4活性的影响  

Effects of acute exposure to high altitude on hepatic function and CYP1A2 and CYP3A4 activities in rats

作　　者：李文斌[1] 贾正平[1] 谢华[1] 张娟红[1] 王延玲[1] 郝颖[1] 王荣[1] 

机构地区：[1]兰州军区兰州总医院全军高原环境损伤防治重点实验室,甘肃兰州730050

出　　处：《南方医科大学学报》2014年第8期1203-1206,共4页Journal of Southern Medical University

基　　金：国家科技部重大资助项目(2008ZXJ09014-010)~~

摘　　要：目的探讨急进高原后影响大鼠药物代谢的肝功能及CYP1A2、CYP3A4活性的变化。方法将健康雄性Wistar大鼠随机分为急进高原组与平原组,眼眶后静脉丛采血后,离心取上清液进行肝功能检测;大鼠麻醉后开腹取大鼠肝脏,进行HE染色观察病理改变;差速离心法提取大鼠肝微粒体,采用P450-GloTM试剂盒,检测肝脏CYP1A2、3A4的活性。结果急进高原组与平原组比较,AST、ALT、ALP分别升高了48.50%、47.90%、103.02%,TP下降了17.80%,差异具有统计学意义(P<0.05);肝组织可见小叶中央静脉水肿,细胞核固缩;急进高原后大鼠CYP1A2、CYP3A4活性分别下降了96.56%和43.53%,差异具有统计学意义(P<0.05)。结论急进高原后大鼠肝脏发生较大损伤,肝微粒体酶的活性显著降低,将在较大程度上影响药物在肝脏的代谢,导致血药浓度升高,半衰期延长,药物的清除率降低。Objective To investigate the changes in hepatic functions and activities of CYPIA2 and CYP3A4 in rats after acute exposure to high altitude. Methods Twelve healthy male Wistar rats were randomly divided into control group and exposure group for acute exposure to normal and high altitude （4010 m） environment. Blood samples were collected from the vena orbitalis posterior for detection of the hepatic function. Hepatic pathologies of the rats were examined microscopically with HE staining. Liver microsomes were extracted by differential centrifugation to assess the activities of CYPIA2 and 3A4 using P450-GloTM kit. Results In rats with acute exposure to high altitude, AST, ALT, and ALP all increased significantly by 48.50%, 47.90%, and 103.02%, respectively, and TP decreased significantly by 17.80% as compared with those in rats maintained in normal altitude environment （P〈0.05）. Pathological examination of the liver revealed edema of the central vein of the liver and hepatocyte karyopyknosis in rats after acute exposure to high altitude, which also resulted in significantly lowered activities of CYPIA2 and 3A4 in the liver （by 96.56% and 43.53%, respectively）. Conclusion Acute exposure to high altitude can cause obvious liver injuries and lowered activities of CYPIA2 and 3A4 in rats to severely affect drug metabolism in the liver and result in increased concentration, prolonged half-life and reduced clearance of drugs.

关 键 词：急进高原 肝功能 CYP1A2 CYP3A4 

分 类 号：R594.3[医药卫生—内科学]