Liver regeneration models in growing animals with portal vein stenosis or hepatic artery ligation: histological, immunohistochemical and molecular studies: evaluation of the effects of insulin and Tacrolimus as regenerative agents

Abstract

The increasing number of transplantations of liver segments or lobes in children has been responsible for growing the interest for the knowledge of liver regeneration. Postoperative vascular complications as portal vein thrombosis/stenosis and hepatic artery thrombosis may lead to biliary complications and retransplantation for liver failure in up to 10% of cases. Drugs with pro-regenerative effect as insulin and tacrolimus may be beneficial in such situations. This work aim to create a model of liver regenetation in growing rats with prejudice of arterial and portal flow, simulating children submitted to liver transplantation and vascular complications. Besides, effects of insulin and tacrolimus in this model will be studied. Weaning rats will be divided in 6 groups according to the kind of intervention: group 1- laparotomy (controls); group 2- resection of 70% of liver parenchyma; group 3- liver resection + portal vein stenosis; group 4- liver resection + hepatic artery ligature; group 5- liver resection + portal stenosis + insulin administration; group 6- liver resection + portal stenosis + tacrolimus administration. Groups 2, 3 and 4 will be subdivided in 5 subgroups according to moment of death: 1, 2, 3, 5 and 10 days after surgical intervention. Groups 5 and 6 will be subdivided in 2 subgroups according to moment of death: 2 and 10 days after intervention. After death, rats will be weighted and their livers will be harvested, weighted and submitted to qualitative histological analysis, determination of mitotic index, imunoistochemical analysis (Ki-67 method) and molecular analysis of expression of interleukin-6 gene. Comparison of survival indexes will be done by means of chi-square and Fisher exact test. Relation between liver and body weight will be analyzed by ANOVA. Histological, imonoistochemical and molecular data will be analyzed by Kruskal-Wallis test. (AU)