Theocharis S E, Margeli A P, Skaltsas S D, Skopelitou A S, Mykoniatis M G, Kittas C N
Department of Histology and Embryology, Medical School, University of Athens, Greece.
Dig Dis Sci. 1997 Sep;42(9):1981-6. doi: 10.1023/a:1018839916535.
The purpose of the present study was to delineate the effect of interferon-alpha2b (IFN-alpha2b) administration on the liver regenerative capacity after partial hepatectomy in rats. The administration of IFN-alpha2b simultaneously with partial hepatectomy did not affect hepatic proliferation in a statistically significant manner. When IFN-alpha2b was administered either 2 or 12 hr postoperatively, an inhibition of hepatocyte proliferation was observed 24 hr postoperatively, while at further time intervals up to 48 hr, DNA synthesis remained similar to that observed in the simply partially hepatectomized rats. The enzyme thymidine kinase (TK), has been implicated in the suppression of proliferation in interferon-treated cell cultures. In all IFN-alpha2b-treated groups of rats, alterations of TK activity were observed without being correlated to the liver regenerative status. Additionally, the administration of the polyamine putrescine in partially hepatectomized rats treated at the time of surgery with IFN strongly enhanced TK activity, but did not affect DNA biosynthesis. In the above-mentioned in vivo model of controlled cellular proliferation, the administration of IFN-alpha2b affected the rate of hepatocyte proliferation depending on the time of its administration; this effect was not correlated to the enzymatic activity of TK, as inhibited TK activity is responsible for the suppressed DNA synthesis in in vitro systems.
本研究的目的是描述α-干扰素2b(IFN-α2b)给药对大鼠部分肝切除术后肝脏再生能力的影响。IFN-α2b与部分肝切除术同时给药对肝脏增殖没有统计学上的显著影响。当术后2小时或12小时给予IFN-α2b时,术后24小时观察到肝细胞增殖受到抑制,而在长达48小时的进一步时间间隔内,DNA合成与单纯部分肝切除的大鼠相似。胸苷激酶(TK)酶与干扰素处理的细胞培养物中的增殖抑制有关。在所有IFN-α2b处理的大鼠组中,观察到TK活性的改变,但与肝脏再生状态无关。此外,在手术时用IFN处理的部分肝切除大鼠中给予多胺腐胺可强烈增强TK活性,但不影响DNA生物合成。在上述体内细胞增殖控制模型中,IFN-α2b的给药根据给药时间影响肝细胞增殖速率;这种作用与TK的酶活性无关,因为在体外系统中,TK活性受抑制是DNA合成受抑制的原因。