2005 Fiscal Year Final Research Report Summary
Isoflurane protects renal function against ischemia and reperfusion through inhibition of protein kinases, JNK and ERK.
| Project/Area Number |
15591639
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Nagasaki University |
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Principal Investigator |
MOROOKA Hiroaki Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (70230175)
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| Project Period (FY) |
2003 – 2005
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| Keywords | SAPK / JNK / p38 MAPK / Ischemia-Reperfusion / ERK / isoflurane |
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| Research Abstract |
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.
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