Dual cytoprotective effects of splenectomy for small-for-size liver transplantation in rats

Naohisa Kuriyama, Shuji Isaji, Masashi Kishiwada, Ichiro Ohsawa, Takashi Hamada, Shugo Mizuno, Masanobu Usui, Hiroyuki Sakurai, Masami Tabata, Tomomi Yamada

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The problems associated with small-for-size liver grafts (ie, high mortality rates, postoperative complications, and acute rejection) remain critical issues in partial orthotopic liver transplantation (OLT). In association with partial OLT, splenectomy (SP) is a procedure used to reduce the portal pressure. However, the precise effects of SP on partial OLT have been unclear. In this study, using small-for-size liver grafts in rats, we examined the cytoprotective effects of SP on OLT. Liver grafts were assigned to 2 groups: a control group (OLT alone) and an SP group (OLT after SP). SP significantly increased animal survival and decreased liver damage. SP exerted the following cytoprotective effects: (1) it improved hepatic microcirculation and prevented increases in the portal pressure after OLT, (2) it suppressed the hepatic infiltration of neutrophils and macrophages through the direct elimination of splenic inflammatory cells before OLT, (3) it decreased the hepatic expression of tumor necrosis factor α and interleukin-6, (4) it attenuated sinusoidal endothelial injury, (5) it decreased plasma endothelin 1 levels and increased hepatic heme oxygenase 1 expression, (6) it suppressed hepatocellular apoptosis through the down-regulation of hepatic caspase-3 and caspase-8 activity, and (7) it increased hepatic regeneration. In conclusion, SP for small-for-size grafts exerts dual cytoprotective effects by preventing excessive portal vein hepatic inflow and eliminating splenic inflammatory cell recruitment into the liver; this in turn inhibits hepatocellular apoptosis and improves liver regeneration.

Original languageEnglish
Pages (from-to)1361-1370
Number of pages10
JournalLiver Transplantation
Volume18
Issue number11
DOIs
Publication statusPublished - 11-2012

All Science Journal Classification (ASJC) codes

  • Surgery
  • Hepatology
  • Transplantation

Fingerprint Dive into the research topics of 'Dual cytoprotective effects of splenectomy for small-for-size liver transplantation in rats'. Together they form a unique fingerprint.

  • Cite this

    Kuriyama, N., Isaji, S., Kishiwada, M., Ohsawa, I., Hamada, T., Mizuno, S., Usui, M., Sakurai, H., Tabata, M., & Yamada, T. (2012). Dual cytoprotective effects of splenectomy for small-for-size liver transplantation in rats. Liver Transplantation, 18(11), 1361-1370. https://doi.org/10.1002/lt.23519