Association of the IL-6/STAT3 signaling pathway with liver regeneration induced by associating liver partition and portal vein ligation for staged hepatectomy in mice

Abstract:

Objective：To establish a mouse model of associating liver partition and portal vein ligation for staged hepatectomy （ALPPS），and to investigate the association of the interleukin-6（IL-6）/STAT3 signaling pathway with liver regeneration promoted by ALPPS. Methods：A total of 45 BALB/C mice were randomly divided into ALPPS group，portal vein ligation（PVL） group，and sham-operated group（SHAM group），with 15 mice in each group. The PVL group was treated with ligation of the portal vein branches for the left lateral lobe，the right side of the middle lobe，and the right lobe while preserving the blood flow in the portal vein branches for the left side of the middle lobe and the caudate lobe. The ALPPS group was treated with partition of the middle lobe along the demar－cation line in addition to the treatment in the PVL group. The SHAM group was treated by dissociating the liver lobes along the hepatic ligaments. The plasma level of alanine aminotransferase（ALT） was measured to evaluate liver function after ALPPS and PVL. The liver regeneration index was used to evaluate liver regeneration. The expression of Ki-67 protein was measured by immunohistochemistry to evaluate the proliferation of hepatocytes. Western blotting was used to examine the change in the IL-6/STAT3 signaling pathway in liver tissue. Results：At 48 hours after surgery，the ALPPS group had a significantly higher ALT level than the PVL group（P=0.000）；from 48 to 96 hours after surgery，both ALPPS and PVL groups had a reduction in ALT level，and there was no signifi－cant difference in ALT level between the ALPPS group and the PVL group at 96 hours after surgery（P=0.094）. At 48 and 96 hours after surgery，the ALPPS had significantly higher liver regeneration index（P48 h=0.000，P96 h=0.000） and percentage of Ki-67-positive hepatocytes（P48 h=0.001，P96 h=0.000） than the PVL group. At 48 hours after surgery，the ALPPS group had significantly higher expression of IL-6 protein and phosphorylation of STAT3 protein than the SHAM group（PIL-6=0.000，PpSTAT3=0.000） and the PVL group（PIL-6=0.011，PpSTAT3=0.003）. Conclusion：A mouse model of ALPPS was successfully established. Compared with PVL，ALPPS can better promote liver regeneration and the IL-6/STAT3 signaling pathway and is closely associated with ALPSS-mediated liver regener－ation in mice.