Sato S, Shimizu M, Hosokawa T, Saito T, Okabe M, Niioka T, Kurasaki M
Department of Food and Nutrition, Hakodate Junior College, Japan.
Pharmacol Toxicol. 2000 Dec;87(6):292-6. doi: 10.1034/j.1600-0773.2000.pto870609.x.
This study was undertaken in order to investigate the effect of zinc (Zn) administration on induction of Zn-binding metallothionein in rat liver with thioacetamide-induced cirrhosis, and the localization of metallothionein in the liver. Normal and cirrhotic rats received intraperitoneal injections with or without Zn. Subsequently, metal analyses, purification of metallothionein by gel filtration and immunohistochemical assessments of metallothionein were carried out. Although in Zn-injected cirrhotic rats, the Zn contents in the liver and plasma increased significantly depending upon the dose of Zn, the Zn contents in the liver and plasma of the cirrhotic rats were lower than those of normal rats after the same dose of Zn. The results of gel filtration also showed that the levels of Zn-metallothionein in the cirrhotic liver were reduced in comparison with those of the normal liver. By the immunohistochemical method, the presence of metallothionein in the parenchymal areas but not in the fibrotic areas of the cirrhotic liver was confirmed. These results suggested that the induced metallothionein was only located in the parenchymal areas. The metallothionein induced in the parenchymal areas was considered to play a role in protecting the parenchymal cells against the progression of fibrosis, because metallothionein has been thought to be involved in the cellular defense against oxidative stress.
本研究旨在探讨给予锌（Zn）对硫代乙酰胺诱导的大鼠肝硬化肝脏中锌结合金属硫蛋白诱导的影响以及金属硫蛋白在肝脏中的定位。正常大鼠和肝硬化大鼠接受有无锌的腹腔注射。随后，进行了金属分析、通过凝胶过滤纯化金属硫蛋白以及对金属硫蛋白进行免疫组织化学评估。尽管在注射锌的肝硬化大鼠中，肝脏和血浆中的锌含量根据锌剂量显著增加，但相同剂量锌后，肝硬化大鼠肝脏和血浆中的锌含量低于正常大鼠。凝胶过滤结果还表明，与正常肝脏相比，肝硬化肝脏中锌金属硫蛋白的水平降低。通过免疫组织化学方法，证实了肝硬化肝脏实质区域存在金属硫蛋白，而纤维化区域不存在。这些结果表明，诱导的金属硫蛋白仅位于实质区域。实质区域诱导的金属硫蛋白被认为在保护实质细胞免受纤维化进展方面发挥作用，因为金属硫蛋白一直被认为参与细胞对氧化应激的防御。
