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

肝移植后预防肝衰竭的措施：供体肝脏预处理的基本调查

• 批准号: 12670466
• 负责人: ARAI Masahiro
• 金额: $ 2.24万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670466/
• 关键词: LIVER TRASNPLANTATION; ISCHEMIA REPERFUSION; KUPFFER CELLS; SUPEROXIDE; ADENOSINE; ISCHEMIC PRECONDITIONING; 活性酵素

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.

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。

项目成果

Arai M, Thurman RG, and Lemasters JJ.: "Contribution of adenosine A_2 receptors and cyclic adenosine monophosphate to protective ischemic preconditioning of sinusoidal endothelial cells against storage/reperfusion injury in rat livers"Hepatology. 32. 297-

Arai M、Thurman RG 和 Lemasters JJ.：“腺苷 A_2 受体和环磷酸腺苷对大鼠肝脏储存/再灌注损伤的肝窦内皮细胞保护性缺血预处理的贡献”肝病学。

Arai M.: "Ischemic preconditioning decreases superoxide production in Kupffer cells after storage/reperfusion via an adeneside A1 receptor pathway"Hepatology. 32. 249A (2000)

Arai M.：“缺血预处理通过腺苷 A1 受体途径减少储存/再灌注后库普弗细胞中超氧化物的产生”肝病学。

Arai M: "Contribution of adenosine A_2 receptors and cyclic adenosine monophosphate to protective ischemic preconditioning of sinusoidal endothelial cells against storage/reperfusion injury in rat livers"Hepatology. Vol32. No2. 297-302 (2000)

Arai M：“腺苷 A_2 受体和环磷酸腺苷对大鼠肝脏储存/再灌注损伤的肝窦内皮细胞保护性缺血预处理的贡献”肝病学。

Arai M.: "Contribution of adeuosiue Az receptors and cyclic adeuosiue wsuophosphate to protective ischemic preconditiconing of siuusoidal endotuelial cells agaiust stsrage/reperfusion injury in rat livers"Hepatology. 32. 297-302 (2000)

Arai M.：“阿兹受体和环状阿兹磷酸盐对大鼠肝脏中的硅样内皮细胞的保护性缺血预处理的贡献，以抵抗应激/再灌注损伤”肝病学。

Arai M, Thurman RG, and Lemasters JJ.: "Ischemic preconditioning of rat livers against cold storage-reperfusion injury : role of nonparenchymal cells and the phenomenon of heterologous preconditioning"Liver Transpl. 7. 292-9 (2001)

Arai M、Thurman RG 和 Lemasters JJ.：“针对冷藏再灌注损伤的大鼠肝脏缺血预处理：非实质细胞的作用和异源预处理的现象”肝脏移植。