Immunosuppressive Therapy and Preservation in Liver Transplantation

1.肝脏保存：1.低温保存肝脏中磷脂代谢物的P-核磁共振研究。肝脏用Euro-Collins或UW-溶液灌流，迅速切除并在4℃保存。通过^&lt；31&gt；P-核磁共振研究清楚地表明，在两种溶液中保存的肝脏中α-甘油磷酸(α-GP)含量增加，但EC-溶液中α-甘油磷酸(α-GP)含量增加更明显。因此，α-糖蛋白可能反映磷脂降解的程度，并与器官的存活率相关。用抗第VIII因子相关抗原(FRA)免疫组织化学方法检测了UW液和Euro-Collins液保存的肝脏的微血管变化。EC组内皮细胞损伤严重，内皮细胞FRA表达减少。此外，III区的血窦内充满了FRA阳性内容。在UW组，这些改变轻微，仅有少量FRA阳性内容。免疫抑制剂FK506：1.FK506处理大鼠的病理和免疫组织化学检查。FK506连续给药4天，分别于第2、5、7、9、11天处死大鼠，取肝和胰腺，用PLP固定，用抗FRA单抗进行免疫组化染色。肝窦内皮细胞未见损伤，谷草转氨酶、谷丙转氨酶升高不明显。UW组FK506治疗后胰腺血管内皮细胞脱离基底膜，FRA表达消失，血清淀粉酶水平明显升高。停止使用FK506可以逆转这些变化。因此，FK506对胰腺血管内皮细胞有毒性作用，有可能引起胰腺炎。

I. Liver Preservation :1. ^<31>P-NMR Study of Phospholipid Metabolites in Hypothermic-Preserved Liver.Liver was perfused by Euro-Collins- or UW-solution, quickly resected and preserved at 4'C. By the ^<31>P-NMR study, it was clearly demonstrated that alpha-glycerophosphate (alpha-GP) increased in livers preserved in both solutions, but much pronounced in EC-solution. Thus, alpha-GP may reflect the extent of phospholipid degradation and correlate with organ viability.2. Microvascular Changes of the Liver Preserved in UW-solution.Livers preserved in UW solution or in Euro-Collins solution were examined with an immunohistochemical method using anti-Factor VIII related antigen (FRA). In EC group, endothelial cell damages was severe and FRA expression on the endothelium was diminished. Furthermore, sinusoid in zone III was filled with FRA-positive contents. In UW group, these changes were mild and only a few FRA-positive contents were recognized. Thus, UW solution prevents endothelial cell damage and microcirculatory injury in zone III during preservation period.II. Immunosuppressant, FK506 :1. Pathological and Immunohistochemical Examination in the Rat Treated with FK506.Rats were administered FK506 for 4 days, and sacrificed on day 2, 5, 7, 9, and 11. Liver and pancreas were resected, fixed in PLP and immunostained using anti-FRA MoAb. Endothelium of sinusoid was not damaged and the levels of GOT and GPT showed S little increase. However, it was clearly demonstratedin UW group that endothelium of the vessels in pancreas was detached from basement membrane and lost its expression of FRA, and that serum amylase level markedly increased during FK506 administration. These change were reversible by the cessation of the FK506 administration. Thus, FK506 has a toxicity on vascular endothelium of pancreas and that has a possibility to cause pancreatitis.