Moreno M G, Muriel P
Departamento de Farmacología y Toxicología, CINVESTAV-I. P. N., México, D.F., México.
Biochem Pharmacol. 1995 Aug 8;50(4):515-20. doi: 10.1016/0006-2952(95)00154-r.
Fibrosis is a dynamic process associated with the continuous deposition and resorption of connective tissue, mainly collagen. Therapeutic strategies are emerging by which this dynamic process can be modulated. Since interferons are known to inhibit collagen production, the aim of this study was to investigate if the administration of interferon-alpha 2b (IFN-alpha) can restore the normal hepatic content of collagen in rats with established fibrosis. Fibrosis was induced by prolonged bile duct ligation. IFN-alpha (100,000 IU/rat/day; s.c.) was administered to fibrotic rats for 15 days. Bile duct ligation increased liver collagen content 6-fold. In addition, serum and liver markers of hepatic injury increased significantly; liver histology showed an increase in collagen deposition, and the normal architecture was lost, with large zones of necrosis being observed frequently. IFN-alpha administration reversed to normal the values of all the biochemical markers measured and restored the normal architecture of the liver. Our results demonstrated that IFN-alpha is useful in reversing fibrosis and liver damage induced by biliary obstruction in the rat. However, further investigations are required to evaluate the therapeutic relevance of interferons on non-viral fibrosis and cholestasis.
纤维化是一个与结缔组织（主要是胶原蛋白）的持续沉积和吸收相关的动态过程。调节这一动态过程的治疗策略正在涌现。由于已知干扰素可抑制胶原蛋白的产生，本研究的目的是调查给予α-2b干扰素（IFN-α）是否能恢复已形成纤维化的大鼠肝脏中胶原蛋白的正常含量。通过长期胆管结扎诱导纤维化。将IFN-α（100,000 IU/大鼠/天；皮下注射）给予纤维化大鼠15天。胆管结扎使肝脏胶原蛋白含量增加了6倍。此外，肝损伤的血清和肝脏标志物显著增加；肝脏组织学显示胶原蛋白沉积增加，正常结构丧失，经常观察到大片坏死区域。给予IFN-α可使所有测量的生化标志物值恢复正常，并恢复肝脏的正常结构。我们的结果表明，IFN-α可有效逆转大鼠胆管梗阻诱导的纤维化和肝损伤。然而，需要进一步研究以评估干扰素对非病毒性纤维化和胆汁淤积的治疗相关性。
