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

肝脏保存和移植后，再灌注早期出现肝窦内皮细胞损伤和枯否细胞活化，通过微循环障碍导致肝脏大面积坏死。短暂的缺血和再灌注使组织抵抗长时间的缺血，这种现象称为缺血预处理。我们先前报道了缺血预处理减少肝窦内皮细胞损伤和枯否细胞活化，从而提高肝移植后受体的存活率。在基金支持的阶段，我们发现：1）缺血预处理减少储存/再灌注后超氧化物的产生，2）腺苷Al受体拮抗剂预处理可逆转这种作用; 3）腺苷Al受体激动剂灌流可减少肝脏缺血预处理后超氧化物的产生。结论：缺血预处理释放的腺苷通过Al受体途径降低了枯否细胞储存/再灌注后超氧阴离子的产生。我们目前正在研究腺苷是否直接影响枯否细胞或不使用体外模型。

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.