Rabbit model of non-cirrhotic portal fibrosis with repeated immunosensitization by rabbit splenic extract

Abstract

Background : Non-cirrhotic portal fibrosis (NCPF) or idiopathic portal hypertension, a disease of unknown etiology, is a common cause of portal hypertension in developing countries. Attempts to understand the etiopathogenesis of NCPF by developing animal models have been made. We describe a novel approach using repeated injections of rabbit splenic extract that were obtained from a previously primed rabbit, to develop a model of NCPF. Methods : Twenty-eight rabbits (1.5-2.0 kg) were divided into the control (group I, n = 13) and the experimental (group II, n = 15) groups. The supernatant obtained after centrifugation of a 20% splenic homogenate, containing 6 mg protein/mL, was mixed with Freund's complete adjuvant (1:1 ratio) and injected intramuscularly to the recipient rabbits every 2 weeks for 3 months. Portal pressure was measured by inserting a cannula into the gastrosplenic vein. Results : The mean portal pressure in group II was significantly (P < 0.05) higher than group I at 1 (19.4 ± 2.9 vs 10.4 ± 2.2 mmHg), 3 (16.7 ± 1.1 vs 7.2 ± 3.6 mmHg), and 6 (20.3 ± 5.4 vs 10.3 ± 4.8 mmHg) months. The mean splenic weight in group II was significantly (P < 0.05) greater than group I at 1, 3 and 6 months. Histopathology of spleen showed medullary congestion, hemosidrin laden macrophages and mild fibrosis. Liver showed normal hepatocytes with mild portal lymphocytic infiltrates and Kupffer cell hyperplasia. No significant anomalies were observed in the tests of liver function at 1 and 6 months. Conclusions : This animal model showed significant splenomegaly, with persistent rise in portal pressure without hepatic parenchymal injury, quite akin to NCPF seen in humans. This study also proposes that repeated immunostimulation may have an important role in the pathogenesis of NCPF.