解整合素-金属蛋白酶9在阿奇霉素诱导的小鼠急性肝损伤过程中的表达分析  

Analysis the expression of a disintegrin and metalloproteases during acute liver injury in the mice induced by azithromycin

作　　者：李三强[1] 王培智[2] 舒友菊[3] 

机构地区：[1]河南科技大学医学院肝脏损伤与修复分子医学重点实验室,河南洛阳471003 [2]河南中医学院科研处,郑州450008 [3]洛阳理工学院环境工程与化学系,河南洛阳471023

出　　处：《中国临床药理学杂志》2013年第10期762-764,共3页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(U1204802);河南省高校科技创新人才支持计划基金资助项目(13HASTIT025);河南省重点科技攻关基金资助项目(122102310030);河南省教育厅科学技术研究基金资助重点项目(12B310003)

摘　　要：目的研究解整合素-金属蛋白酶9(ADAM9)在阿奇霉素诱导的小鼠急性肝损伤过程中表达的动态变化及作用。方法 50只小鼠随机分为2组:正常组10只,实验组40只。实验组小鼠腹腔注射40 mg·mL-1阿奇霉素溶液6,24,42和72 h,分别摘除小鼠眼球采血,分离2组血清,检测谷丙转氨酸(AST)和谷草转氨酸(ALT)活性;用免疫组化和RT-PCR等方法检测2组不同时间点小鼠肝脏中ADAM9在蛋白和核酸水平的表达变化。结果阿奇霉素注射小鼠后6h,ADAM9的表达量显著下降(P<0.05),表明肝细胞受到损伤;24 h肝脏损伤达到最大程度时,ADAM9的表达量仍然维持在较低水平(P<0.05);24～48 h随着肝脏进行修复和再生,ADAM9的表达逐渐增加,在注射阿奇霉素后42 h达到最大值(P<0.05),然后逐渐恢复到接近正常水平。结论 ADAM9在药物性肝脏损伤和修复过程中可能起到重要的作用。Objective To study the expressed of a disintegrin and metalloproteases（ADAM9 ） during acute liver injury induced by azithromytin. Methods Fifty mice were randomly divided into two groups; normal group （n = 10） and experimental group （n =40）. The mice in experimental group were respectively drawn blood by removing the eyeballs and serum was separated to detect the activity of AST and ALT at 6 h, 24 h, 42 h and 72 h after ip injection with 40 mg·mL- 1 azithromycin. The activity of serum AST and ALT in the mice of normal group was also detected. The expression of hepatic ADAM9 at protein and mRNA levels was detected by immunohistochemistry and RT - PCR in the mice of two groups at different time points after azithromycin injection. Results Hepatocytes were damaged and the expression of ADAM9 were significantly down - regulated （ P 〈 0. 05 ） at 6 h, and the liver injury reached the most degree at 24 h and the expression of ADAM9 still maintained the low level （P 〈 0. 05 ）, but slightly increased compared with that at 6 h after azithromycin injection. Liver began to repair and regenerate during 24 h to 48 h after azithromycin injection. The expression of ADAM9 were gradually increased and reached the maximum at 42 h （ P 〈 0. 05 ） and then recovered to the normal level after azithromycin injection. Conclusion ADAM9 were remarkably differently expressed during acute liver injury induced by azithromyein, which indicated that ADAM9 may play important roles during druginduced liver injury and repair.

关 键 词：阿奇霉素 急性肝损伤 表达 免疫组化法 

分 类 号：R978.1[医药卫生—药品] R969.3[医药卫生—药学]