Margeli Alexandra P, Papadimitriou Lila, Ninos Sotirios, Manolis Evangelos, Mykoniatis Michael G, Theocharis Stamatios E
Department of Experimental Pharmacology, University of Athens, Medical School, Department of Clinical Biochemistry, Aghia Sophia Children's Hospital, Athens, Greece.
Liver Int. 2003 Jun;23(3):171-8. doi: 10.1034/j.1600-0676.2003.00828.x.
AIMS/BACKGROUND: Hepatic stimulator substance (HSS) is a liver-specific growth factor implicated in hepatocellular proliferation and hepatoprotection in models of acute liver injury. In the present study, we examined the effect of exogenous HSS administration on liver proliferating capacity and survival outcome in an experimental animal model of fulminant hepatic failure (FHF) and encephalopathy, induced by repeated injections of thioacetamide (TAA) in rats.
Fulminant hepatic failure was induced in adult male Wistar rats by three consecutive intraperitoneal injections of TAA (400 mg/kg of body weight), at 24 h time intervals. The animals received intraperitoneally either a saline solution or HSS (50 mg protein/kg of body weight), 2 h after the second and third TAA injections. The animals were killed at 6, 12 and 18 h post the last injection of TAA.
Levels of liver enzymes and urea in serum, blood ammonia values, liver histology, stage of hepatic encephalopathy and survival were statistically significantly improved in TAA-intoxicated and HSS-treated rats compared to TAA-intoxicated and saline-treated ones. Furthermore, HSS ameliorated liver regenerative indices--DNA biosynthesis, thymidine kinase activity and hepatocyte mitotic activity--in a statistically significant manner.
Our data suggest the beneficial effect of HSS administration in this animal model of FHF and encephalopathy, supporting evidence for a possible use of HSS as supportive therapy, by increasing hepatocellular proliferation, in management of FHF.
目的/背景：肝刺激物质（HSS）是一种肝脏特异性生长因子，在急性肝损伤模型中与肝细胞增殖和肝脏保护有关。在本研究中，我们在大鼠反复注射硫代乙酰胺（TAA）诱导的暴发性肝衰竭（FHF）和肝性脑病实验动物模型中，研究了外源性给予HSS对肝脏增殖能力和生存结局的影响。
成年雄性Wistar大鼠通过每隔24小时连续3次腹腔注射TAA（400mg/kg体重）诱导暴发性肝衰竭。在第二次和第三次TAA注射后2小时，动物腹腔内注射生理盐水或HSS（50mg蛋白/kg体重）。在最后一次注射TAA后6、12和18小时处死动物。
与TAA中毒并接受生理盐水治疗的大鼠相比，TAA中毒并接受HSS治疗的大鼠血清肝酶和尿素水平、血氨值、肝脏组织学、肝性脑病分期及生存率均有统计学显著改善。此外，HSS以统计学显著方式改善了肝脏再生指标——DNA生物合成、胸苷激酶活性和肝细胞有丝分裂活性。
我们的数据表明给予HSS在该FHF和肝性脑病动物模型中具有有益作用，支持HSS可能作为支持性治疗用于FHF管理中以增加肝细胞增殖的证据。
