Gribilas Georgios, Zarros Apostolos, Zira Athina, Giaginis Costas, Tsourouflis Gerasimos, Liapi Charis, Spiliopoulou Chara, Theocharis Stamatios E
Department of Forensic Medicine and Toxicology, Medical School, National and Kapodistrian University of Athens, Goudi, 11527 Athens, Greece.
Dig Dis Sci. 2009 Nov;54(11):2367-76. doi: 10.1007/s10620-008-0623-1. Epub 2008 Dec 10.
Liver fibrosis results from sustained wound healing response to chronic liver injury. Liver cirrhosis, the end stage of the fibrotic process, is characterized by disruption of the entire liver architecture and reduced hepatocyte regenerative ability. Hepatic stimulator substance (HSS) is a liver-specific growth factor triggering hepatocyte proliferation in vitro and in vivo. Previous studies have indicated the involvement of HSS in animal models of acute liver injury. The aim of the present study was to investigate the involvement of HSS in the process of fibrosis and cirrhosis induction. Liver fibrosis and cirrhosis were induced in rats by thioacetamide (TAA) administration (300 mg/l) in the drinking water for 3 months, and animals were killed at 0, 1, 2, and 3 months of treatment. TAA administration resulted in progressively increasing liver fibrosis, leading to the onset of cirrhosis at the end of the experimental time. HSS was continuously produced during the course of fibrosis and cirrhosis induction, peaking at the 2nd month of TAA treatment, coinciding with markers of hepatic proliferative capacity, as thymidine kinase activity and DNA biosynthesis. Significantly reduced HSS activity was noted in cirrhotic liver (3rd month). In this case, the exogenous HSS administration during the 3rd month of TAA treatment suppressed the onset of liver cirrhosis, stimulating the hepatic regenerative capacity. Our data indicate the active participation of HSS in the process of fibrosis and cirrhosis induction post-TAA treatment in rats, suggesting also the beneficial effect of HSS treatment against cirrhosis induction with future possible clinical implications.
肝纤维化是对慢性肝损伤持续的伤口愈合反应的结果。肝纤维化的终末期肝硬化的特征是整个肝脏结构遭到破坏以及肝细胞再生能力降低。肝刺激物质（HSS）是一种肝脏特异性生长因子，可在体外和体内触发肝细胞增殖。先前的研究表明HSS参与急性肝损伤的动物模型。本研究的目的是调查HSS在纤维化和肝硬化诱导过程中的作用。通过在饮水中给予硫代乙酰胺（TAA，300mg/L）3个月来诱导大鼠肝纤维化和肝硬化，并在治疗的0、1、2和3个月处死动物。给予TAA导致肝纤维化逐渐加重，在实验末期引发肝硬化。在纤维化和肝硬化诱导过程中持续产生HSS，在TAA治疗的第2个月达到峰值，这与肝脏增殖能力的标志物如胸苷激酶活性和DNA生物合成一致。在肝硬化肝脏（第3个月）中观察到HSS活性显著降低。在这种情况下，在TAA治疗的第3个月给予外源性HSS可抑制肝硬化的发生，刺激肝脏再生能力。我们的数据表明HSS积极参与大鼠TAA治疗后纤维化和肝硬化的诱导过程，这也提示HSS治疗对肝硬化诱导具有有益作用，可能具有未来的临床意义。
