MEASURES AGAINST HEPATIC FAILURE AFTER LIVER TRANSPLANTATION : BASIC INVESTIGATION ON PRECONDITIONING OF THE DONOR LIVER

在肝脏保存和移植过程中，再灌流早期出现肝窦内皮细胞损伤和库普弗细胞活化，通过微循环障碍导致肝脏大量坏死。短暂的缺血和再灌注使组织对长时间的缺血具有抵抗力，这一现象称为缺血预适应。我们先前报道，缺血预适应减少肝窦内皮细胞损伤和库普弗细胞激活，从而提高肝移植受者的存活率。在赠款支持的时期内，我们发现)缺血预适应减少保存/再灌流后超氧化物歧化产物的产生，2)腺苷Al受体拮抗剂的预适应，3)腺苷Al激动剂肝灌流减少保存/再灌流后超氧化物的产生。结论：缺血预适应时释放的腺苷通过Al受体途径减少库普弗细胞保存/再灌流后超氧化物歧化产物的产生。我们目前正在使用体外模型研究腺苷是否直接影响Kupffer细胞。

When liver is stored and transplanted, sinusoidal endothelial cell injury and activation of Kupffer cells appeared in the early phase of reperfusion, leading to massive hepatic necrosis via microcirculatory disturbance. A brief period of ischemia and reperfusion render tissues resistant against prolonged ischemia, a phenomenon called ischemic preconditioning. We previously reported that ischemic preconditioning decreases sinusoidal endothelial cell injury and Kupffer cell activation, and as the result, improves recipient survival after liver transplantation.In the supported period by the grant, we revealed that l) ischemic preconditioning decreases superoxide production after storage/reperfusion, 2) this effect is reversed by pretreatment with adenosine Al receptor antagonist and 3) liver perfusion with adenosine Al agonist decreases superoxide production after storage/reperfusion like ischemic preconditioning. It is concluded that adenosine released during preconditioning ischemia decreases superoxide production by Kupffer cells after storage/reperfusion via Al receptor pathway. We are at present investigating whether adenosine directly affects Kupffer cells or not using in vitro model.