Fort J, Pilette C, Veal N, Oberti F, Gallois Y, Douay O, Rosenbaum J, Calès P
Laboratoire d'Hémodynamique Splanchnique, Bordeaux, France.
J Hepatol. 1998 Aug;29(2):263-70. doi: 10.1016/s0168-8278(98)80012-3.
BACKGROUND/AIMS: The aim of this study was to assess the effect of the early and chronic administration of interferon alpha in the prevention of hepatic fibrosis and portal hypertension.
Rats with liver fibrosis due to bile duct ligation or CCl4 were divided into three groups: sham, placebo and interferon alpha2a 100,000 UI/day. Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and mRNA (fibronectin, procollagen alpha2(I)) contents, and serum hyaluronate. Systemic and splanchnic hemodynamics were also evaluated.
Interferon alpha significantly decreased fibrosis in the CCl4 model only: area of fibrosis: 13.9+/-3.7 vs 10.5+/-3.3% (p<0.05), hydroxyproline: 1.8+/-0.6 vs 1.2+/-0.2 mg/g wet liver (p<0.001), respectively placebo vs interferon alpha. There was a significant correlation between the area of fibrosis and hydroxyproline liver content (r=0.77 in the biliary model and r=0.87 in the CCl4 model, p<0.0001). Interferon decreased spleno-renal shunt blood flow (2.0+/-1.8 vs 0.9+/-0.7 ml/min; p<0.05) but not portal pressure in the CCl4 model. No significant effects were observed in rats with biliary fibrosis.
The early and chronic administration of interferon alpha prevents the development of liver fibrosis and porto-collateral circulation in the CCl4 model but not in the biliary model. However, the antifibrotic effects of interferon need to be confirmed in further studies.
背景/目的：本研究旨在评估早期和长期给予α干扰素对预防肝纤维化和门静脉高压的作用。
将因胆管结扎或四氯化碳导致肝纤维化的大鼠分为三组：假手术组、安慰剂组和α干扰素2a 100,000 UI/天组。通过纤维化面积（图像分析）、肝脏羟脯氨酸和mRNA（纤连蛋白、前胶原α2（I））含量以及血清透明质酸评估肝纤维化。还评估了全身和内脏血流动力学。
α干扰素仅在四氯化碳模型中显著降低纤维化：纤维化面积：安慰剂组与α干扰素组分别为13.9±3.7% vs 10.5±3.3%（p<0.05），羟脯氨酸：1.8±0.6 vs 1.2±0.2 mg/g湿肝（p<0.001）。纤维化面积与肝脏羟脯氨酸含量之间存在显著相关性（胆管模型中r = 0.77，四氯化碳模型中r = 0.87，p<0.0001）。在四氯化碳模型中，α干扰素降低了脾肾分流血流量（2.0±1.8 vs 0.9±0.7 ml/min；p<0.05），但未降低门静脉压力。在胆管纤维化大鼠中未观察到显著影响。
早期和长期给予α干扰素可预防四氯化碳模型中肝纤维化和门体侧支循环的发展，但不能预防胆管模型中的发展。然而，干扰素的抗纤维化作用需要在进一步研究中得到证实。
