Inoue Takeshi, Horiai Haruo, Aoki Chizuru, Kawamura Ikuo, Ota Mariko, Mizuhara Hidekazu, Tomoi Masaaki, Mutoh Seitaro
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6, Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
In Vivo. 2003 May-Jun;17(3):293-9.
The aim of this study was to evaluate the effect of insulin-like growth factor-I (IGF-I) on lethality and liver function in experimental acute liver failure. Intravenous co-administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) to rats induced high mortality and marked increases in aspartate aminotransferase, alanine aminotransferase and total bilirubin, associated with hypoglycemia. One-hour pre-treatment with IGF-I significantly prevented lethality and blood parameter changes in rats. Histological examination also showed that massive hepatocellular hemorrhagic necrosis and inflammatory cell infiltration around peri-central veins in the liver, as well as shrinkage of cytoplasm and nuclear condensation, were induced by GalN plus LPS injection, but these all were improved by pre-treatment with IGF-I. Overall, this study showed that IGF-I treatment resulted in effective prevention of lethal acute liver failure in rats induced by GalN plus LPS, suggesting a therapeutic potential for IGF-I in the prevention of acute liver failure.
本研究的目的是评估胰岛素样生长因子-I(IGF-I)对实验性急性肝衰竭大鼠致死率和肝功能的影响。给大鼠静脉联合注射D-半乳糖胺(GalN)和脂多糖(LPS)可导致高死亡率,并使天冬氨酸转氨酶、丙氨酸转氨酶和总胆红素显著升高,同时伴有低血糖。IGF-I预处理1小时可显著预防大鼠的致死率及血液参数变化。组织学检查还显示,GalN加LPS注射可诱导肝脏中央静脉周围出现大量肝细胞出血性坏死和炎性细胞浸润,以及细胞质收缩和核浓缩,但IGF-I预处理可改善这些情况。总体而言,本研究表明,IGF-I治疗可有效预防GalN加LPS诱导的大鼠致死性急性肝衰竭,提示IGF-I在预防急性肝衰竭方面具有治疗潜力。