Evidence that graft survival is not related to parenchymal cell viability in rat liver transplantation. The importance of nonparenchymal cells.
Evidence that graft survival is not related to parenchymal cell viability in rat liver transplantation. The importance of nonparenchymal cells.
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有证据表明，大鼠肝移植中移植物存活与实质细胞活力无关。
DOI：
10.1097/00007890-198909000-00023
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发表时间：
1989
期刊：
影响因子：
6.2
通讯作者：
Thurman,RG
中科院分区：
文献类型：
--
作者：
Marzi,I;Zhong,Z;Lemasters,JJ;Thurman,RG
损伤的实质和非实质细胞的肝脏储存在冷的欧洲柯林斯解决方案进行了评估后再灌注，并与移植物存活率进行比较大鼠原位肝移植。通过台盼蓝拒染法（97%的细胞）和储存后再灌注20分钟的肝脏的LDH释放（4%的总）评估，在长达24小时的冷藏后，实质细胞几乎完全保持其活力。此外，肝糖酵解（乳酸加丙酮酸生产率），摄氧量和NADH氧化还原状态（乳酸：丙酮酸比）在所有时间点研究的正常范围内，冷藏24小时。相比之下，非实质细胞在储存8小时后开始失去活力，如台盼蓝染色所评估：储存24小时后40%无活力。由于非实质细胞的损伤仅发生在再灌注时，因此可能涉及氧自由基。因此，黄嘌呤和次黄嘌呤，氧自由基形成的底物，测量灌注液再灌注。随着储存时间的推移，两种嘌呤都积累（高达80 [mu] M），并在再灌注时迅速（< 10分钟）被冲洗掉。虽然实质细胞的功能是在正常范围内的肝脏储存在寒冷的24小时，肝脏移植物储存6小时和更长的时间在欧洲柯林斯解决方案不能移植成功。因此，我们得出结论，肝移植前肝实质细胞的活力是一个很差的参数来预测移植的结果。因此，实质细胞能量状态的评估（例如，用31 P NMR和其他方法）很可能不能可靠地预测存活率。另一方面，非实质细胞在储存和再灌注后明显更早地失去其活力。这些数据表明，保存非实质细胞的活力是成功的肝移植的关键。
Injury to parenchymal and nonparenchymal cells of livers stored in cold Euro-Collins solution was assessed following reperfusion and compared with graft survival following orthotopic rat liver transplantation. Parenchymal cells maintained their viability nearly completely after up to 24 hr of cold storage as assessed by trypan blue exclusion (97% of cells) and LDH release (4% of total) from livers reperfused for 20 min following storage. Furthermore, hepatic glycolysis (rates of lactate plus pyruvate production), oxygen uptake and NADH redox state (Iactate: pyruvate ratio) were in the normal range at all time points studied up to 24 hr of cold storage. In contrast, nonparenchymal cells lost viability as assessed from trypan blue staining beginning after 8 hr of storage: 40% were nonviable after 24 hr of storage. Since injury to nonparenchymal cells occurs only upon reperfusion, oxygen radicals may be involved. Accordingly, xanthine and hypoxanthine, substrates for oxygen radical formation, were measured in perfusate upon reperfusion. Both purines accumulated (up to 80 [mu] M) with time of storage and were washed out rapidly (< 10 min) upon reperfusion. Although parenchymal cell function was in the normal range in livers stored in the cold for 24 hr, liver grafts stored for 6 hr and longer in Euro-Collins solution could not be transplanted successfully. Thus, we conclude that viability of parenchymal cells in liver grafts prior to transplantation is a poor parameter to predict the outcome of transplantation. Therefore, assessment of parenchymal cell energy state (eg, with 31 P NMR and other methods) most likely will not predict survival reliably. On the other hand, nonparenchymal cells lose their viability significantly earlier following storage and reperfusion. These data suggest that preservation of nonparenchymal cell viability is critical for successful liver transplantation.