Association Of The MDA5 Signaling Pathway With Liver Regeneration Induced By Associating Liver Partition Staged Hepatectomy In Mice

Objective: To establish a mice model of associating liver partition and portal vein ligation for staged hepatectomy(ALPPS),and to investigate the effects of melanoma differentiation associated gene-5(MDA5)signaling pathway on liver cell regeneration during ALPPS operation.To provide reference and guidance for the mature development of ALPPS.Methods:Sixty C57/BL6 mice were randomly divided into three groups: ALPPS(combined with in situ portal vein ligation)operation group,PVL(portal vein ligation)operation group,and SHAM(SHAM operation)group,with a sample size of 20 in each group,and they were divided into corresponding groups.After the mice were anesthetized,a midabdominal incision was made into the abdomen,and the liver of the mice was fully exposed by blunt separation of the falcate liver ligament and the hepatogastric ligament.The corresponding arterial branch,bile duct branch and portal vein branch of the caudate lobe,right lobe and middle lobe of the liver of the mice were separated clearly.The SHAM group was sutured directly after the above procedures.The portal vein branches of left lateral lobe,right middle lobe and right lobe were ligated in PVL group.In the ALPPS group,on the basis of the PVL group,the middle lobe of the liver was severed along the ischemia line generated by portal vein ligation.The expression changes of TNF-α and MDA5 under the influence of different surgical methods were detected by Western Blot,and the liver regeneration index under different groups was measured.The hypertrophy and regeneration of cells in the liver were observed by HE staining of liver sections,and the liver regeneration was evaluated by combining the former two methods.Immunohistochemical method was used to detect the expression of Ki-67 positive protein in the liver to evaluate the proliferation of liver cells.Results: The liver regeneration index(P<0.05)and the average number of hepatocytes per field in ALPPS group were higher than those in PVL group on the4 th and 7th day after surgery(P<0.05).The expression of TNF-α and the proportion of Ki67-positive cells in ALPPS group were higher than those in PVL group on postoperative day 2,and there were statistical differences between ALPPS group and PVL group(P<0.05).TNF-α was similar between ALPPS and PVL on the 4th and 7th day after operation(P BBB 0 0.05).The expression of MDA5 in ALPPS group on the 2nd,4th and 7th day after surgery was higher than that in Sham group and PVL group(P<0.05).Conclusion: The mice ALPPS model was successfully established.ALPPS was more effective in promoting liver regeneration than PVL,and the MDA5 signaling pathway was closely related to the ALPPS mediated liver regeneration process.