苯巴比妥、反式氧化茋和3-甲基胆蒽对大鼠肝小叶中心、中间和汇管区环氧水解酶的影响。

Effects of phenobarbital, trans-stilbene oxide, and 3-methylcholanthrene on epoxide hydrolase within centrilobular, midzonal, and periportal regions of rat liver.

作者信息

Kawabata T T, Guengerich F P, Baron J

出版信息

J Biol Chem. 1983 Jun 25;258(12):7767-73.

Abstract

The effects of phenobarbital, trans-stilbene oxide, and 3-methylcholanthrene on epoxide hydrolase (EC 3.3.2.3) within centrilobular, midzonal, and periportal hepatocytes were investigated employing rabbit anti-serum produced against rat hepatic microsomal epoxide hydrolase in unlabeled antibody peroxidase-anti-peroxidase and indirect fluorescent antibody-staining techniques. In livers of control rats, midzonal and periportal hepatocytes bound the anti-epoxide hydrolase to similar extents while centrilobular hepatocytes bound approximately 25% more antibody. 3-Methylcholanthrene did not cause significant alterations in immunohistochemical staining for epoxide hydrolase within any region of the liver lobule, whereas phenobarbital and trans-stilbene oxide produced significant alterations in both the intensity and pattern of intralobular staining for the enzyme. After 4 days of phenobarbital pretreatment, anti-epoxide hydrolase binding to hepatocytes was slightly, but significantly, elevated, especially within midzonal regions. After 7 days of phenobarbital pretreatment, anti-epoxide hydrolase binding was increased by approximately 65% within midzonal regions and by approximately 41 and 24%, respectively, within centrilobular and periportal regions. In livers of trans-stilbene oxide-pretreated rats, anti-epoxide hydrolase binding was increased by approximately 80% within both the midzonal and periportal regions and by approximately 43% within centrilobular regions. These immunohistochemical findings demonstrate that phenobarbital and trans-stilbene oxide both induce epoxide hydrolase nonuniformly within the liver lobule. However, while phenobarbital induces the enzyme to the greatest extent within midzonal hepatocytes and to the least extent within periportal hepatocytes, trans-stilbene oxide induces epoxide hydrolase equally within midzonal and periportal hepatocytes.

摘要

采用抗大鼠肝微粒体环氧化物水解酶的兔抗血清，运用未标记抗体过氧化物酶-抗过氧化物酶和间接荧光抗体染色技术，研究了苯巴比妥、反式氧化芪和3-甲基胆蒽对中央小叶、中区和门周肝细胞内环氧化物水解酶（EC 3.3.2.3）的影响。在对照大鼠的肝脏中，中区和门周肝细胞结合抗环氧化物水解酶的程度相似，而中央小叶肝细胞结合的抗体量大约多25%。3-甲基胆蒽在肝小叶的任何区域均未引起环氧化物水解酶免疫组化染色的显著改变，而苯巴比妥和反式氧化芪均使该酶在小叶内的染色强度和模式发生了显著改变。苯巴比妥预处理4天后，抗环氧化物水解酶与肝细胞的结合略有但显著升高，尤其是在中区区域。苯巴比妥预处理7天后，中区区域抗环氧化物水解酶的结合增加了约65%，中央小叶和门周区域分别增加了约41%和24%。在反式氧化芪预处理大鼠的肝脏中，中区和门周区域抗环氧化物水解酶的结合均增加了约80%，中央小叶区域增加了约43%。这些免疫组化结果表明，苯巴比妥和反式氧化芪均在肝小叶内非均匀地诱导环氧化物水解酶。然而，苯巴比妥在中区肝细胞中诱导该酶的程度最大，在门周肝细胞中诱导程度最小，而反式氧化芪在中区和门周肝细胞中同等程度地诱导环氧化物水解酶。