Simultaneous bile duct and portal vein ligation induces faster atrophy/hypertrophy complex than portal vein ligation: role of bile acids.

Weizheng Ren,Xiaofeng Wang,Chonghui Li,Wenping Lv,Aiqun Zhang,Jia-Hong Dong,Ke Pan,Geng Chen

doi:10.1038/srep08455

Weizheng Ren, Xiaofeng Wang + Show 6 more

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https://doi.org/10.1038/srep08455

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Abstract

Portal vein ligation (PVL) induces atrophy/hypertrophy complex (AHC). We hypothesised that simultaneous bile duct and portal vein ligation (BPL) might induce proper bile acid (BA) retention to enhance AHC by activating BA-mediated FXR signalling in the intact liver and promoting apoptosis in the ligated liver. We established rat models of 90% BPL and 90% PVL and found that BPL was well-tolerated and significantly accelerated AHC. The enhanced BA retention in the intact liver promoted hepatocyte proliferation by promoting the activation of FXR signalling, while that in the ligated liver intensified caspase3-mediated apoptosis. Decreasing the BA pools in the rats that underwent BPL could compromise these effects, whereas increasing the bile acid pools of rats that underwent PVL could induce similar effects. Second-stage resection of posterior-caudate-lobe-spearing hepatectomy was performed 5 days after BPL (B-Hx), PVL (V-Hx) or sham (S-SHx), as well as whole-caudate-lobe-spearing hepatectomy 5 days after sham (S-Hx). The B-Hx group had the most favourable survival rate (93.3%, the S-SHx group 0%, the S-Hx group 26.7%, the V-Hx group 56.7%, P < 0.01) and the most sustained regeneration. We conclude that BPL is a safe and effective method, and the acceleration of AHC was bile acid-dependent.

Highlights

Portal vein ligation (PVL) induces atrophy/hypertrophy complex (AHC)
We hypothesised that simultaneous bile duct and portal vein ligation (BPL) might induce proper bile acid (BA) retention to enhance AHC by activating BA-mediated FXR signalling in the intact liver and promoting apoptosis in the ligated liver
Apoptosis as indicated by caspase 3 cleavage was prominent throughout observation, consistently higher than in the PVL group (Fig. 6I). These results showed that alleviating the BA retention induced by BPL resulted in compromised AHC, while enhancing the BA retention after PVL induced similar effect as BPL, suggesting that the enhanced intrahepatic BA retention was the main reason for the difference between BPL and PVL

Summary

Introduction

We hypothesised that simultaneous bile duct and portal vein ligation (BPL) might induce proper bile acid (BA) retention to enhance AHC by activating BA-mediated FXR signalling in the intact liver and promoting apoptosis in the ligated liver. The enhanced BA retention in the intact liver promoted hepatocyte proliferation by promoting the activation of FXR signalling, while that in the ligated liver intensified caspase3-mediated apoptosis. BA retention in the ligated liver might promote the apoptosis-mediated atrophy, which could, in turn, further promote regeneration of the intact liver. We hypothesise that BPL could induce stronger AHC via activating BA-mediated FXR signalling in the intact liver and promoting apoptosis in the ligated liver. We established rat models of BPL and PVL and compared their effects in inducing AHC and the tolerance of a hypertrophied liver with second-stage extended hepatectomy. The role of BAs in enhancing AHC was examined more directly in rats in which BA pools were either increased or decreased when they received PVL/BPL

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