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New strategy for a successful liver transplantation from uncontrolled non-heart-beating donors (NHBD) or using extremely small for size grafts

来自不受控制的无心跳供体 (NHBD) 或使用极小尺寸移植物的成功肝移植的新策略

基本信息

批准号：
15390369
负责人：
SATOMI Susumu
金额：
$ 8万
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：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

We have developed new strategy for a successful liver transplantation from uncontrolled non-heart-beating donors (NHBD) or using extremely small for size grafts.A.Rats were divided into five groups as follows ; 1)HB : livers were retrieved from heart-beating donors 2)NHB : livers were retrieved from NHBD 3)NM : from NHBD pretreated with nafamostat mesilate 4)FR : from NHBD pretreated with FR167653 5)FR+NM : from NHBD pretreated with FR167653 and nafamostat mesilate. In the NHB group, the values of IL-1β, TNF-a, thromboxane B2, leukotriene B4, and expressions of NF-κB, AP1, and cyclooxygenase-2 were significantly higher than those in the HB group. But in the FR+NM group those values were low, the structure of sinusoids was preserved and sinusoidal lumen was maintained histologically, the same findings were observed in the HB group. This combined treatment was quite effective in preserving sinusoid microcirculation in the liver grafts from NHBD.B.We performed orthotopic liver transplanta … More tion using grafts from NHBD pretreated with nafamostat mesilate, FR167653 and OP2507(PGI2 analog : PG). Rats were divided into eight groups as follows ; 1)Control : without treatment 2)FR+PG+NM 3)FR+PG 4)FR+NM 5)PG+NM 6)FR 7)PG 8)NM. In the FR+PG+NM group and the FR+PG group, survival rate was significantly improved compared to the control group and the structure of sinusoids was preserved histologically. These combined treatments were quite effective in liver transplantation from NHBD.C.Using pigs, the right lateral lobe, i.e. the 25% of the liver, was transplanted orthotopically. Pigs were divided into two groups ; graft without portacaval shunt (PCS)(n=11), and graft with PCS(n=11). Survival rate, portal flow, hepatic arterial flow and histological findings were investigated. The portal flow after transplantation in the group without PCS were increased 2.4 times, but the arterial flow were decreased. In the group without PCS, all pigs except for one died of liver dysfunction within 24 hours after transplantation. On the other hand, in the group with PCS, the portal flow were decreased after transplantation, but the arterial flow were increased 1.5 times. In the group with PCS, eight pigs survived for more than 4 days. These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury. Less

A)大鼠分为五组：1)HB：取自心脏跳动供体的肝脏；2)NHB：取自NHBD；3)NM：取自NHBD；4)FR：取自NHBD；4)FR：取自FR167653；5)FR+NM：取自NHBD；非血瘀组IL-1β、肿瘤坏死因子-α、血栓素B2、白三烯B4及核因子-κB、活化蛋白1、环氧合酶-2的表达均显著高于非血瘀组。而FR+NM组上述指标均较低，在组织学上仍保留了窦结构和窦腔，HB组也有相同的表现。这种联合治疗在保存非高压性肝病患者移植肝的肝窦微循环方面非常有效。我们进行了原位肝移植…。更多地使用经甲磺酸那法莫司特、FR167653和OP2507(PGI2类似物：PG)处理的NHBD移植物。大鼠分为8组：1)对照组：未处理2)FR+PG+NM 3)FR+PG 4)FR+NM 5)PG+NM 6)FR 7)PG 8)NM。FR+PG+NM组和FR+PG组的存活率明显高于对照组，且组织学上仍保留了血窦结构。这些综合治疗在NHBDC的肝脏移植中非常有效。使用猪，将右外侧叶，即25%的肝脏进行原位移植。将猪分为两组：无门腔分流术(PCS)组(n=11)和门腔静脉分流组(PCS)。观察存活率、门脉血流量、肝动脉血流量及组织学改变。无PCS组移植后门静脉血流量增加2.4倍，但动脉血流量减少。在没有PCS的组中，除一头外，所有猪在移植后24小时内死于肝功能障碍。PCS组移植后门脉血流量减少，但动脉血流量增加1.5倍。在PCS组中，8头猪存活了4天以上。这些结果表明，门静脉血流过多是由于肝窦微循环损伤导致的极小体积肝移植术后肝功能障碍所致。较少