Development for Anti-Cytokine Therapy on Hepatic Graft Reperfusion Injury.

肝移植物再灌注损伤的抗细胞因子疗法的发展。

基本信息

批准号：
07407034
负责人：
KITAJIMA Masaki
金额：
$ 9.22万
依托单位：
KEIO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

Inflammatory cytokines, interleukin (IL)-l and tumor necrosis factor (TNF), may play an important role in hepatic ischemia-reperfusion (I/R) injury. To study the role of IL-l in hepatic I/R injury, we investigated the effect of pretreatment with IL-l receptor antagonist (IL-1ra) on the production of IL-l and TNF,histological findings in the liver, and the survival rate for 7 days. The animals were subjected to 90 min of warm liver ischemia by clamping the portal vein and hepatic artery of the left and middle lobes. In the IL-lra-treated group, IL-lra was given 5 min before inducing liver ischemia. IL-la (ELISA) and TNF (L929) were determined in blood and liver at 0,30,90, and 180 min post-reperfusion. In addition, at 180 min post-reperfusion the damaged (left lateral and median lobes) and non-damaged (right lateral and caudate lobes) livers were removed respectively for IL-la and TNF determination. In another experiment to determine the effect of IL-lra pretreatment on survival rate fo … More r 7 days, after 90 min of liver ischemia, the vessels were released and the right lateral and caudate lobes were excised, leaving only the ischemic left lateral and median lobes. In both groups, IL-la was undetectable in blood, but was increased in liver tissue. TNF increased in both blood and liver tissue as reperfusion time increased. The histological findings were minimal in the IL-lra-treated group even at 180 min post-reperfusion. Furthermore, in the IL-lra-treated group, the production of TNF was decreased in both blood and liver tissue as compared with that in the non-treated group. At 180 min post-reperfusion, damaged liver produced significantly more IL-la and TNF than the non-damaged liver. Survival rates in the IL-lra-treated group and in the non-treated group were 80% (8/10) and 30% (6/20), respectively. The data demonstrated that the production of IL-l and TNF increases in hepatic I/R injury and that pretreatment with IL-lra protects the liver from ischemic insult, indicating the important role of IL-l in I/R injury. Less

炎症细胞因子白细胞介素 (IL)-1 和肿瘤坏死因子 (TNF) 可能在肝缺血再灌注 (I/R) 损伤中发挥重要作用。为了研究 IL-1 在肝 I/R 损伤中的作用。研究了IL-1受体拮抗剂(IL-1ra)预处理对IL-1和TNF产生的影响、肝脏组织学结果以及7天的存活率。通过夹紧左叶和中叶的门静脉和肝动脉来进行90分钟的热肝缺血。在IL-lra治疗组中，在诱导肝缺血之前5分钟给予IL-lra。再灌注后0、30、90和180分钟测定血液和肝脏中的TNF(L929)。另外，再灌注后180分钟测定受损区域。在另一项实验中，分别切除（左侧叶和中叶）和未受损（右侧叶和尾叶）肝脏进行 IL-1a 和 TNF 测定，以确定 IL-1ra 预处理对存活率的影响。天，肝缺血90分钟后，释放血管并切除右侧叶和尾状叶，仅留下缺血的左侧叶和正中叶。在两组中，IL-1α均被释放。在血液中检测不到，但在肝组织中TNF随着再灌注时间的增加而增加，即使在再灌注后180分钟，组织学结果也很少。与未治疗组相比，-1ra治疗组的血液和肝组织中TNF的产生均减少。再灌注后180分钟，受损肝脏产生的IL-1α和TNF明显多于未治疗组。 IL-1ra治疗组和未治疗组的未受损肝脏的存活率分别为80%（8/10）和30%（6/20）。数据表明IL的产生。 -l和TNF在肝I/R损伤中增加，并且用IL-lra预处理可以保护肝脏免受缺血性损伤，表明IL-1在I/R损伤中的重要作用。