Effects of tacrolimus and insulin in a liver regeneration model in growing animals with portal vein stenosis: immunohistochemical and molecular studies.
The aim of the present investigation was to describe a new model of liver regeneration in growing rats with reduced portal flow. In addition, it was studied whether tacrolimus and insulin could have any pro-regenerative effect under such conditions. Ninety-five rats were divided into five groups: Group 1 (sham), abdominal incision without intervention; Group 2, 70% hepatectomy; Group 3, 70% hepatectomy + PV stenosis; Group 4, 70% hepatectomy + portal vein stenosis + insulin; and Group 5, 70% hepatectomy + portal vein stenosis + tacrolimus. The remnant liver lobes were harvested for analyses. The liver weight decreased in the PV stenosis group and it increased with the use of insulin and tacrolimus. The mitotic activity was higher in the hepatectomy, insulin and tacrolimus groups and this parameter was reduced by portal stenosis. Levels of interleukin 6 (IL-6) were higher in the hepatectomy group compared to the sham and PV stenosis groups. The expression of IL-6 and Ki67 was significantly increased in the insulin and tacrolimus groups compared to the portal stenosis group. A highly reproducible model was standardized to study liver regeneration with portal blood inflow reduction in weaning rats. It was demonstrated that insulin or tacrolimus administration may partially reverse the harmful effects of PV stenosis.
Pediatric Surgery Division, Pediatric Liver Transplantation Unit and Laboratory of Research in Pediatric Surgery (LIM 30), University of Sao Paulo Medical School, Sao Paulo, Brazil.
Ariane Nadia
AN
Backes
Ana Cristina Aoun
AC
Tannuri
Fabiane Neiva
FN
Backes
Amadeu Jose Rodrigues
AJ
Queiroz
Maria Cecília Mendonça
MC
Coelho
Elenice Lima
EL
da Silva
Evandro Sobroza
ES
de Mello
Uenis
U
Tannuri
D000818:Animals; D065095:Calcineurin Inhibitors / Q000494:pharmacology*; D003251:Constriction, Pathologic; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics; D008099:Liver / Q000098:blood supply; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D016133:Polymerase Chain Reaction; D011169:Portal Vein / Q000473:pathology*; D012313:RNA / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D016559:Tacrolimus / Q000494:pharmacology*
D065095:Calcineurin Inhibitors; D007328:Insulin; D015850:Interleukin-6; D012313:RNA; D016559:Tacrolimus