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The experimental study about liver grafts from Marginal Donor

边缘供肝移植的实验研究

基本信息

批准号：
17390343
负责人：
SATOMI Susumu
金额：
$ 9.79万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Background. For a successful liver transplantation (LTx) from non-heart-beating donors (NHBD), it is necessary to clarify the mechanism of the liver grafts injuries. In this study we investigated the effects of pre-cold preservation perfusion on the grafts for the purpose of the maintenance of the energy status and microcirculation. We also investigated the effects of the antioxidant, biliverdin, and free radical scavenger, edaravone on liver grafts to reduce inflammatory reaction.Methods. Male Wistar rats were used. Livers were retrieved, preserved in UW solution, and perfused for ) 60 minutes with oxygenated Krebs-Henseleit solution. Rats were allocated to six groups as follows (n=5) : i)Control group; no warm ischemia (WI) and cold preservation, ii)HBD group; no WI with cold preservation for 6 hours, iii)NHBD group; with 30 minutes of WI and cold preservation, iv)PRE group ; with WI, 30 minutes pre-cold preservation perfusion after cardiac arrest, and cold preservation, v)BV group; addition of biliverdin to pre-cold preservation perfusion, vi)ED group; addition of biliverdin to pre-cold preservation perfusion. Portal flow and bile production during reperfusion, AST and TNF-α in perfusate, energy charge (EC) and ATP level in the tissue, and histological findings were investigated.Results. Portal flow volume in the PRE, ED, and BV groups were higher than in NHBD group. Bile production in the PRE, ED, and BV groups were also higher than in the NHBD group. Increase of AST and TNF-a was reduced in the BV group. EC and ATP level of the BV group after reperfusion were higher than those of the NHBD group.Conclusions. Pre-cold preservation perfusion and addition of edaravone or biliverdin to perfusate improved viability of grafts from NHBD. The results mean that to preserve the energy status and microcirculation of the graft is important for successful LTx from NHBD.

背景无心跳供者肝移植的成功，需要明确供肝损伤的机制。本研究旨在探讨预冷保存灌注对移植物能量状态和微循环的影响。我们还研究了抗氧化剂胆绿素和自由基清除剂依达拉奉对肝移植物的影响，以减少炎症反应。使用雄性Wistar大鼠。取出肝脏，保存在UW溶液中，并用充氧的Krebs-Henseleit溶液灌注60分钟。将大鼠分为6组（n=5）：i）对照组;无热缺血（WI）冷保存组; ii）HBD组;无WI冷保存6 h组; iii）NHBD组; WI冷保存30 min组; iv）PRE组;在预冷保存灌注中加入胆绿素，vi）艾德组：在预冷保存灌注中加入胆绿素。观察再灌注期门静脉血流量、胆汁生成量、灌注液中AST、TNF-α、组织中能荷（EC）、ATP含量及组织学改变。PRE、艾德、BV组门静脉血流量均高于NHBD组。PRE、艾德和BV组的胆汁生成也高于NHBD组。BV组AST、TNF-α升高幅度明显低于对照组。BV组再灌注后EC和ATP水平高于NHBD组。预冷保存灌注和加入依达拉奉或胆绿素灌注可提高NHBD移植物的存活率。结果表明，保持移植物的能量状态和微循环是NHBD成功LTx的重要因素。