A new experimental animal model: contradictory atrophic and regenerative stimuli by combination of portal vein ligation and partial hepatectomy

Background: Portal vein ligation (PVL) leads to atrophy of dependent liver lobes and hypertrophy of intact liver lobes, while partial hepatectomy (PHx) leads to hyperplasia of residual liver lobes. It is unclear that how the portal flow deprived-liver lobes adjust its size under the proliferative stimulus induced by PH. In this study we investigated the size regulation of individual liver lobe in the combined model- PVL+PHx.

Material and methods: We established new rodent model of 20% PVL+70% PHx and 70% PVL+20% PHx respectively. Liver lobe size regulation were evaluated 1, 2, 3 and 7 after operation in terms of liver lobe weight and hepatocyte proliferation. 20% PVL, 20% PH, 70% PHx, 70% PVL and sham operation were performed as controls.

Results: Ligated right lobe had a 30% growth with moderate proliferation after 20% PVL+70% PHx, but the ligated lobes (LLL and ML) after 70% PVL+ 20% PHx shrank to 50% of its original size (low proliferation), while the ligated lobe after 20% PVL or 70% PVL shrank to 30% (no proliferation). CL in both combined groups grew to 4 fold size showing prolonged proliferation, whereas 3 fold after 70% PHx following a typical proliferative activity.

Conclusion: The atrophic stimulus can be buffered by the proliferative stimulus induced by PHx. The size regulation of portally-deprived lobe depends on the balance of the two contradictory stimuli. This finding suggests a global “size-sensing mechanism” of the liver as expressed in the metabolic load hypothesis.

Keywords: PVL, PHx, proliferation, liver size regulation