Isoflurane protects renal function against ischemia and reperfusion through inhibition of protein kinases, JNK and ERK.

异氟醚通过抑制蛋白激酶、JNK 和 ERK 来保护肾功能免受缺血和再灌注的影响。

基本信息

批准号：
15591639
负责人：
MOROOKA Hiroaki
金额：
$ 1.79万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Ischemia/reperfusion injury (IRI) is a major problem in the surgery. Isoflurane has a pharmacological preconditioning effect against IR in the heart and brain, but whether this also occurs in the kidney is still unclear. In this study, we tested the hypothesis that isoflurane had a protective effect against IRI in the rat kidney, and further that JNK inhibition contributed this protective effect.Animals were randomly divided into four groups. Group F underwent sham surgery only. Group G received 1.5% isoflurane before sham surgery. Groups H and I were subjected to 40-min left renal ischemia by clamping the renal pedicles. Group I received 1.5% isoflurane for 20 min before renal ischemia. Ischemic kidneys were harvested at 0, 5, 40 and 90 min after starting reperfusion, and sham kidneys were harvested at 40 min after sham surgery, for measurement of JNK activities.JNK was markedly activated as early as 5 min after starting reperfusion, with a peak at 40 min, and remained at a relatively high level until 90 min after starting reperfusion in group H (ischemia only). The activity of JNK in group I (with isoflurane) was significantly lower than in group H from 40 to 90 min after starting reperfusion. We conclude that isoflurane has a protective effect against renal IRI when administered before ischemia and that the effect would involve the inhibition of JNK.

缺血/再灌注损伤（IRI）是手术中的主要问题。异氟烷在心脏和大脑中具有针对IR的药理预处理作用，但是肾脏中是否也发生这种情况。在这项研究中，我们检验了异氟烷对大鼠肾脏中IRI具有保护作用的假设，此外，JNK抑制作用促进了这种保护作用。动物被随机分为四组。 F组仅接受假手术。 G组在假手术前接受了1.5％的异氟烷。 H组和我通过夹紧肾脏椎弓根，将左肾脏缺血左肾脏缺血。我的组在肾脏缺血之前收到1.5％的异氟烷。开始再灌注后0、5、40和90分钟收获缺血性肾脏，并在假手术后40分钟收获假肾脏，以测量JNK活动。JNK在开始再灌注后5分钟在启动再灌注后5分钟被显着激活，并在40分钟后以相对较高的高度保持较高的水平，直到启动次数为90分钟，直至组成次数，直至组合（均为90分钟）。 JNK在开始再灌注后40至90分钟的I组（与异氟烷）中的活性显着低于H组的活性。我们得出的结论是，在缺血之前给药时，异氟烷对肾脏IRI具有保护作用，其作用将涉及JNK的抑制作用。