Fort J, Oberti F, Pilette C, Veal N, Gallois Y, Douay O, Rousselet M C, Rosenbaum J, Calès P
Laboratoire d'Hémodynamique Splanchnique, Université d'Angers, Bordeaux, France.
Hepatology. 1998 Dec;28(6):1525-31. doi: 10.1002/hep.510280612.
The aim of this study was to assess the effect of the early and chronic administration of octreotide in the prevention of hepatic fibrosis and portal hypertension (PHT). Two experimental models of liver fibrosis caused by bile duct ligation (BDL) or CCl4 were divided into 4 rat groups: sham, placebo, and octreotide (10 and 100 micrograms/kg twice daily, subcutaneously). Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and fibronectin mRNA contents, and serum hyaluronate. Systemic and splanchnic hemodynamic changes were also evaluated, including the splenorenal shunt blood flow by the transit-time ultrasound (TTU) technique. In both models, splenorenal shunt blood flow was significantly lower in the octreotide groups than in the placebo group (P <.05), while portal pressure was not significantly decreased. There was a significant decrease in fibrosis by octreotide in the CCl4 model only: area of fibrosis: 13.9% +/- 3.7% vs. 9.8% +/- 2.5% (P <.01), hydroxyproline: 1.8 +/- 0.6 vs. 1.3 +/- 0.4 mg/g wet liver (P <.05), respectively, placebo vs. octreotide 10 micrograms/kg. There was a significant correlation between the area of fibrosis and hydroxyproline liver content (r =.87 in the biliary model and r =.91 in the CCl4 model; P <.0001). The early and chronic administration of octreotide prevents the development of portocollateral blood flow without reducing portal pressure in two models of liver fibrosis and the development of liver fibrosis in the CCl4 model.
本研究的目的是评估早期和长期应用奥曲肽预防肝纤维化和门静脉高压（PHT）的效果。将胆管结扎（BDL）或四氯化碳（CCl4）所致的两种肝纤维化实验模型分为4组大鼠：假手术组、安慰剂组和奥曲肽组（10和100微克/千克，每日两次，皮下注射）。通过纤维化面积（图像分析）、肝脏羟脯氨酸和纤连蛋白mRNA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变化，包括通过渡越时间超声（TTU）技术测定脾肾分流血流量。在两种模型中，奥曲肽组的脾肾分流血流量均显著低于安慰剂组（P<.05），而门静脉压力未显著降低。仅在CCl4模型中，奥曲肽可使纤维化显著减轻：纤维化面积：安慰剂组与奥曲肽10微克/千克组分别为13.9%±3.7% vs. 9.8%±2.5%（P<.01），羟脯氨酸：分别为1.8±0.6 vs. 1.3±0.4毫克/克湿肝（P<.05）。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=.87，CCl4模型中r=.91；P<.0001）。在两种肝纤维化模型中，早期和长期应用奥曲肽可预防侧支血流的形成，但不降低门静脉压力，且在CCl4模型中可预防肝纤维化的发展。
