Study of using small-for-size fatty liver graft for liver transplantation

采用小型脂肪肝移植进行肝移植的研究

基本信息

批准号：
21791279
负责人：
MIZUNO Shugo
金额：
$ 2.58万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2012
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791279/
关键词：
肝移植脂肪肝過小グラフト生体肝移植過少グラフト

项目摘要

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 hepaticexpression of tumor necrosis factor a 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.

与小尺寸的肝移植物相关的问题（即高死亡率，术后并发症和急性排斥）在部分原位肝移植（OLT）中仍然是关键问题。与部分OLT相关，脾切除术（SP）是一种用于降低门户压力的程序。但是，SP对部分OLT的确切影响尚不清楚。在这项研究中，使用大鼠中的小肝移植物，我们检查了SP对OLT的细胞保护作用。将肝移植物分配给2组：对照组（单独使用OLT）和一个SP组（SP后OLT）。 SP显着增加了动物存活率并减少肝脏损害。 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 hepaticexpression of tumor necrosis factor a and interleukin-6, (4) it衰减的正弦内皮损伤，（5）它降低了血浆内皮素1水平并增加了肝血红素氧酶1的表达，（6）它通过下调肝caspase-3和caspase-8和（7）IT抑制了肝细胞凋亡，并增加了肝脏的恢复。总之，SP用于小型移植物，通过防止过度的门静脉肝流入和消除脾脏炎性细胞募集到肝脏中，从而发挥双重细胞保护作用；反过来，这抑制了肝细胞凋亡并改善肝脏再生。