Effects of tacrolimus and insulin in a liver regeneration model in growing animals with portal vein stenosis: immunohistochemical and molecular studies

Author(s)

Backes, Ariane Nadia ^{[1, 2]} ; Aoun Tannuri, Ana Cristina ^{[1, 2]} ; Backes, Fabiane Neiva ^{[1, 2]} ; Rodrigues Queiroz, Amadeu Jose ^{[1, 2]} ; Mendonca Coelho, Maria Cecilia ^{[1, 2]} ; da Silva, Elenice Lima ^{[1, 2]} ; de Mello, Evandro Sobroza ^[3] ; Tannuri, Uenis ^{[4, 1, 2]}

Affiliation

^[1] Univ Sao Paulo, Div Pediat Surg, Pediat Liver Transplantat Unit, Sch Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Lab Res Pediat Surg LIM 30, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Liver Funct Res Lab LIM 14, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, BR-01246903 Sao Paulo - Brazil

• Document type: Journal article
• Source: PEDIATRIC SURGERY INTERNATIONAL; v. 30, n. 4, p. 423-429, APR 2014.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 12/04122-0 - 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
• Grantee: Ana Cristina Aoun Tannuri
• Support Opportunities: Regular Research Grants