Studies on the mechanism and treatment of ischemia-reperfusion injury of the liver

肝脏缺血再灌注损伤的机制及治疗研究

基本信息

批准号：
02454317
负责人：
NAGASUE Naofumi
金额：
$ 4.48万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

Ischemia and reperfusion of the liver are innevitable processes in hepatic transplantation. How are various types of hepatic injury produced by ischemia deteriorate or ameliorate by reperfusion ? This question was studied in terms of intrahepatic calcium level, oxgen derived free radicals and mitochondrial function. In addition, the effects of cyclosporin A and FK506 and Verapamil were investigated in terms of these parameters. The following results were obtained by this study.(1) Changes in tissue calcium during ischemia and reperfusion of the liver Ca^<2+> in the liver did not change during ischemia but was immediately elevated after reperfusion. The elevated Ca^<2+> was soon expelled from the liver when the ischemic time was short. Upon prolonged ischemia, hepatic Ca^<2+> was reelevated, which was related to the extent of tissue injury and animal death. The release of superoxide did not play a major role in the changes of Ca^<2+> level.(2) Role of the Kupffer cell in ischemia-reperf … More usion injury of the liver More severe tissue injury was found after ischemia-reperfusion when Kupffer cells were preliminarily activated by zymosan. TNF alpha and beta were not involved in the process, but increased production of superoxide seemed to play an important role.(3) Plasma activities of lysosomal enzymes in porcine liver transplantation After liver grafting in pigs, plasma activities of beta-galactosidase, beta-glucosidase and beta-glucuronidase increased with their peaks at 3 hours, which returned to normal within 2 to 3 days. These changes reflected the severity of liver injury well.(4) Effects of cyclosporin A and FK506 on ischemia-reperfusion injury of the liver Pretreatment with these two drugs showed a protective effect on ischemia-reperfusion injury of the canine and porcine livers. The effect seemed to be mediated through lysosomal stabilization and protection of mitochondrial morphology and function.(5) Effect of Verapamil on prolonged liver ischemia and reperfusion Despite numerous works reporting the beneficial effect of Verapamil on liver ischemia, this drug was not effective on 180 minute warm ischemia, showing that the effect of Verapamil differs according to the ischemic time. Less

在陪审团中，陪审团中的肝类型的肝类型的缺血过程是根据epripriccium级别的辞职来研究的。参数的术语。在缺血期间的组织钙的变化和肝脏在肝脏中的融资没有变化，但在延长的静脉缺血时，肝脏中没有变化。被重新升级，这与组织和动物死亡的程度有关。参与过程，但增加了超氧化物的产生，起着重要作用。这些变化反映了肝脏的严重性。肝脏缺血的维拉帕米根据缺血时间差异