Shiratori Y, Kawase T, Shiina S, Okano K, Sugimoto T, Teraoka H, Matano S, Matsumoto K, Kamii K
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Hepatology. 1988 Jul-Aug;8(4):815-21. doi: 10.1002/hep.1840080420.
In an attempt to elucidate the role of hepatic macrophages in liver injury, we investigated galactosamine-treated rats (500 mg per kg body weight). The rats received an i.v. injection of latex particles (2 x 10(9) particles per animal) prior to (latex-galactosamine) or 12 to 16 hr subsequent to the galactosamine treatment (galactosamine-latex). Effect of superoxide dismutase on hepatic injury induced by galactosamine or galactosamine-latex treatment was also examined. Oxygen-derived free radical-generating capacity of isolated hepatic macrophages was measured as chemiluminescence with the stimulation of phorbol myristate acetate or latex particles. As compared with normal rats, chemiluminescence of hepatic macrophages from galactosamine-treated rats was 5- to 10-fold enhanced 12 hr following galactosamine treatment and remained elevated for 48 hr. Chemiluminescence of the latex particle-pretreated macrophages in the liver was markedly suppressed even following the galactosamine treatment (p less than 0.01). Compared to galactosamine-treated rats, both lipid peroxide level in the liver tissue and AST and ALT concentration in serum were significantly decreased in the latex-galactosamine-treated rats (p less than 0.01) and increased in the galactosamine-latex-treated rats (p less than 0.01). Furthermore, superoxide dismutase supplementation protected against liver injury induced by the galactosamine-latex treatment. From these results, pretreatment with latex particles suppressed the free radical-generating capacity of hepatic macrophages and protected against hepatic injury induced by galactosamine. In contrast, injection of latex particles after galactosamine treatment aggravated hepatic injury, which was prevented by superoxide dismutase. These data suggest that liver injury induced by galactosamine is modulated by oxygen-derived free radicals from hepatic macrophages.
为了阐明肝巨噬细胞在肝损伤中的作用，我们研究了用半乳糖胺处理的大鼠（每千克体重500毫克）。大鼠在半乳糖胺处理前（乳胶-半乳糖胺组）或半乳糖胺处理后12至16小时（半乳糖胺-乳胶组）接受静脉注射乳胶颗粒（每只动物2×10⁹个颗粒）。还研究了超氧化物歧化酶对半乳糖胺或半乳糖胺-乳胶处理诱导的肝损伤的影响。通过在佛波酯肉豆蔻酸酯或乳胶颗粒刺激下的化学发光来测量分离的肝巨噬细胞产生氧衍生自由基的能力。与正常大鼠相比，半乳糖胺处理的大鼠肝巨噬细胞的化学发光在半乳糖胺处理后12小时增强了5至10倍，并持续升高48小时。即使在半乳糖胺处理后，肝脏中预先用乳胶颗粒处理的巨噬细胞的化学发光也明显受到抑制（p<0.01）。与半乳糖胺处理的大鼠相比，乳胶-半乳糖胺处理的大鼠肝组织中的脂质过氧化物水平以及血清中的AST和ALT浓度均显著降低（p<0.01），而半乳糖胺-乳胶处理的大鼠则升高（p<0.01）。此外，补充超氧化物歧化酶可预防半乳糖胺-乳胶处理诱导的肝损伤。从这些结果来看，预先用乳胶颗粒处理可抑制肝巨噬细胞产生自由基的能力，并预防半乳糖胺诱导的肝损伤。相反，在半乳糖胺处理后注射乳胶颗粒会加重肝损伤，而超氧化物歧化酶可预防这种损伤。这些数据表明，半乳糖胺诱导的肝损伤受肝巨噬细胞产生的氧衍生自由基调节。
