Muriel P
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del I.P.N. México, D.F. México.
J Hepatol. 1996 May;24(5):614-21. doi: 10.1016/s0168-8278(96)80148-6.
BACKGROUND/AIMS: Interferons have been used to treat chronic viral hepatitis, due to their antiviral properties. However, interferons are now recognized also to inhibit collagen production. Since fibrosis has been associated with liver damage and dysfunction, the effects of interferon-alpha 2 b on biliary obstruction-induced fibrosis were investigated.
Extrahepatic cholestasis was induced in male Wistar rats (around 200g) by double ligation and division of the common bile duct. Control rats were sham operated. Interferon-alpha 2b (IFN-alpha; 100,000 IU/rat) was administered subcutaneously, daily after surgery. The animals were killed after 4 weeks of bile duct ligation or sham operation. Liver damage and cholestasis was analyzed by histological, ultrastructural and biochemical techniques.
Biliary obstruction produced dilation of the bile canaliculi, disorganization of mitochondria and an increase in vacuolization. Bile duct ligation led to an important accumulation of collagen, determined, both histologically and as the hydroxyproline content of the liver. Bilirubin and serum enzyme activities (determined as markers of cholestasis) increased several-fold after bile duct ligation. Administration of IFN-alpha to bile duct ligated rats resulted in significant preservation of ultrastructure, histology, inhibition of collagen accumulation and in a partial improvement of serum markers of cholestasis.
It is concluded that interferons possess interesting beneficial effects on the liver not related to its antiviral properties but probably associated with its antifibrogenic properties.
背景/目的：由于干扰素具有抗病毒特性，已被用于治疗慢性病毒性肝炎。然而，现在人们也认识到干扰素能抑制胶原蛋白的产生。鉴于纤维化与肝损伤和功能障碍有关，本研究探讨了α-2b干扰素对胆管梗阻所致肝纤维化的影响。
通过双重结扎和切断胆总管，在雄性Wistar大鼠（约200g）中诱导肝外胆汁淤积。对照组大鼠进行假手术。术后每天皮下注射α-2b干扰素（IFN-α；100,000IU/只大鼠）。胆管结扎或假手术后4周处死动物。采用组织学、超微结构和生化技术分析肝损伤和胆汁淤积情况。
胆管梗阻导致胆小管扩张、线粒体排列紊乱和空泡化增加。胆管结扎导致肝脏胶原大量积聚，这在组织学检查以及肝脏羟脯氨酸含量测定中均得到证实。胆管结扎后胆红素和血清酶活性（作为胆汁淤积的标志物测定）增加了几倍。给胆管结扎大鼠注射IFN-α可显著保留超微结构、组织学结构，抑制胶原积聚，并部分改善胆汁淤积的血清标志物。
得出结论，干扰素对肝脏具有有趣的有益作用，这些作用与其抗病毒特性无关，而可能与其抗纤维化特性有关。
