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

缺血和肝脏的再灌注是肝移植中不可避免的过程。通过再灌注会探测缺血或改善各种类型的肝损伤？该问题是根据肝内钙水平，氧气衍生自由基和线粒体功能进行了研究的。另外，研究了这些参数的环孢菌素A和FK506和Verapamil的影响。通过这项研究获得了以下结果。（1）缺血期间组织钙的变化和肝脏中肝Ca^<2+>的再灌注在缺血期间没有改变，但在再灌注后立即升高。当缺血时间短时，升高的Ca^<2+>很快被从肝脏中排出。长时间的缺血后，重新升级了肝脏Ca^<2+>，这与组织损伤和动物死亡的程度有关。超氧化物的释放在Ca^<2+>水平的变化中没有主要作用。（2）库普弗细胞在缺血 - 培养官中的作用……在肝脏恢复性损伤的情况更严重的肝脏损伤时，当kupffer细胞被Zymosan最初激活时，会发现更严重的组织损伤。 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 天。这些变化很好地反映了肝损伤的严重程度。（4）环孢菌素A和FK506对这两种药物的肝脏预处理缺血再灌注损伤的影响表明对犬类和猪猪的缺血再灌注损伤具有保护作用。 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 minutes warm ischemia, showing that the effect of Verapamil differs according to the ischemic time.