Elucidation of Mechanism in primary graft nonfunction of transplanted fatty liver graft and detection of methods preventing the mechanism

1.用适度（30 - 60%）脂肪的脂肪肝制作动物模型，我们可以用富含胆固醇的食物来喂养人类脂肪肝，使它接近等于吃脂肪肝。对线粒体ATP合成的测试比较脂肪肝脏模型（F-模型）到正常模型（N-模型）关于肝脏组织ATP、能量电荷和质子ATP酶的活动，在它们之间没有显著差异。对肉桂线细胞（SLCs）的伤害进行测试，以澄清SLCs的伤害，我们测量了血液的半胱氨酸（HA），并将其与F型模型相比较。F型模型中的HA明显高于N型模型中的HA，所以我建议F型模型中的SLCs比N型模型中的那些更脆弱。整个肥胖的肝脏移植的结果已被发现并储存在1， 6， 12小时的冷UW解决方案中。在储存后，我们移植了移植了正确的和比较了用脂肪肝移植的老鼠的生存率，用正常肝脏移植。当所有带有正常肝脏移植的食谱在超过一周的时间内存活下来时，带有肥胖肝脏移植的食谱在6小时内储存了40%，在12小时内储存了0%。在6小时后，ATP合成的Mitochondrial能力在脂肪和正常肝脏移植之间并没有明显的区别，但在重新渗透脂肪肝脏移植的SLCs的损害比正常肝脏移植的严重性更大。为预防再灌注问题准备药物（1）将Kuppfer细胞用于治疗强烈影响的再灌注问题， L-DMDP是用捐赠者处理的，（2）将抑制PLA R-D22 R-D2在再灌注中的活性， Liver移植将用Nafamostat介质（NM）注射溶液进行治疗。However，带有肥胖的liver的老鼠并没有被改善为生存的准备。

1. Making an animal modelAs a rat model with a moderately (30〜60%) fatty liver, we could make it nearly equal to human fatty liver by feeding the rat with cholesterol-rich meal.2. Examination of mitochondrial ATP synthesisCompared fatty liver model (F-model) to normal model (N-model) about liver tissue ATP, energy charge, and the activity of proton ATPase, there were no significant differences among them.3. Examination of injury of sinusoidal lining cells (SLCs)To clarify injury of SLCs, we measured hyaluronic acid (HA) of blood and compared it in F-model to it in N-model. HA in F-model was significantly higher than in N-model, so it was suggested that SLCs of F-model was more fragile than those of N-model.4. Results of liver transplantationWhole fatty liver was resected and was stored in cold UW solution for 1, 6, 12 hours. After storage, we transplanted the graft orthotopically and compared survival rate of rat with fatty liver graft to that with normal liver graft. While all of the recipients with normal liver grafts survived for more than one week, survival rate at one week of recipients with fatty liver grafts stored in 6 hours was 40% and that in 12 hours was 0%. Mitochondrial ability of ATP synthesis after 6 hour-storage was not significantly different between fatty and normal liver graft, but after repurfusion the injury of SLCs of fatty liver graft was severer than that of normal graft.5. Preparation of drugs for preventing reperfusion injury(1) To eliminate Kuppfer cells which strongly affected repurfusion injury, L-DMDP was pretreated in donors, and (2) to inhibit PLAィイD22ィエD2 activity at repurfusion, liver graft was rinsed with Nafamostat mesilate (NM) rinse solution. However, the rats with fatty liver grafts were not improved to survive by preparation of either drug.