ROLE OF SUPEROXIDE FROM MACROPHAGES IN HEPATIC FIBROSIS

本项目旨在探讨巨噬细胞超氧化物在肝纤维化过程中的作用。得到了以下结果：1)二甲基亚硝胺致肝纤维化大鼠注射含有羟基脯氨酸的阿拉伯胶后，巨噬细胞肿胀，形成空泡，沿增加的肝纤维堆积。阿拉伯胶刺激大鼠腹腔巨噬细胞释放超氧化物，使肝胶原合成减少。对于其他多糖和乳胶颗粒，则没有这样的发现。2)注射超氧化物歧化酶对二甲基硝基胺大鼠肝胶原合成无影响。由此可见，巨噬细胞可能在肝纤维化中发挥抑制胶原合成的作用。阿拉伯胶给药后活化巨噬细胞积累的意义还有待研究。由于体内超氧化物在胶原合成中的作用尚未得到证实，体外实验应使用分离的肝成纤维细胞与来自不同肝损伤的Kupffer细胞共培养系统进行。

The aim of this project is to investigate a role of superoxide from macrophages in the process of hepatic fibrosis.The following results have been obtained.1) When rats with hepatic fibrosis induced by dimethylnitrosamine administration received injections of arabic gum, a polysaccharide with hydroxyproline, macrophages swollen with vacuoles accumulated along increased hepatic fibers. Hepatic collagen synthesis was reduced after arabic gum adnimistration which stimulated rats to release superoxide from peritoneal macrophages. In case of other polysaccharides and latex particles, there was no such findings.2) Superoxide dismutase injections did not affect hepatic collagen synthesis in rats given dimethylnitosamine.From these, macrophages might play a role in inhibiting collagen synthsis in hepatic fibrosis. The significance of activated macrophages accumulated after arabic gum administration remains to be investigated. As the role of superoxide in collagen synthesis has not been proved in vivo, experiments in vitro should be carried out using a co-culture system of isolated hepatic fibroblasts with Kupffer cells from varying liver injuries.