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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.

与小体积肝移植相关的问题（即高死亡率，术后并发症和急性排斥反应）仍然是部分原位肝移植（奥尔特）的关键问题。与部分奥尔特相关，脾切除术（SP）是一种用于降低门静脉压力的手术。然而，SP对部分奥尔特的确切影响尚不清楚。在这项研究中，使用小体积的大鼠肝移植，我们研究了SP对奥尔特的细胞保护作用。移植肝分为两组：对照组（单独奥尔特）和SP组（SP后奥尔特）。SP显著增加动物存活率和降低肝损伤。SP具有以下细胞保护作用：（1）改善肝微循环，防止奥尔特后门静脉压力升高，（2）通过直接清除脾内炎性细胞，抑制中性粒细胞和巨噬细胞向肝内浸润，（3）降低肝组织肿瘤坏死因子α和白细胞介素-6的表达，（4）减轻肝窦内皮损伤，（5）降低血浆内皮素1水平和增加肝血红素氧合酶1表达，（6）通过下调肝caspase-3和caspase-8活性抑制肝细胞凋亡，和（7）增加肝再生。总之，小尺寸移植物的SP通过防止过多的门静脉肝流入和消除脾脏炎性细胞募集到肝脏中来发挥双重细胞保护作用;这反过来又抑制肝细胞凋亡并改善肝再生。