2000 Fiscal Year Final Research Report Summary
The role of heat shock proteins in ischemic acute renal failure
| Project/Area Number |
10671416
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Anesthesiology/Resuscitation studies
|
|---|
| Research Institution | OKAYAMA UNIVERSITY |
|---|
Principal Investigator |
TAKAHASHI Toru Okayama University, Medical School, Assistant Professor, 医学部, 助手 (40252952)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HIRAKAWA Masahisa Okayama University, Medical School, Professor, 医学部, 教授 (70033058)
AKAGI Reiko Okayama Prefectural University, Associate Professor, 保健福祉学部, 助教授 (50150967)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Keywords | ischemic acute renal failure / heme oxygenase-1 / heat shock protein 70 / δ-aminolevulinate synthase / tin mesoporphyrin / heme / renal function / oxidative stress |
|---|
| Research Abstract |
Objective : The aim of this study was to examine the role of heme oxygenase-1 (HO-1) induction in the recovery of renal function in rat with ischemic acute renal failure (IARF).
Design : Randomized, masked, controlled animal study.
Setting : University-based animal research facility.
Subjects : Sprague-Dawley male rats, weighing 200 to 250g.
Interventions : Aneslhetized rats were subjected to bilateral flank incisions, and the right kidney was removed. Renal ischemia was performed by left renal microvascular clamping, followed by reflow of the blood.
Measurements and Main Results : Ischemia of the kidney in the uninephrectomized rat significantly induced HO-1 mRNA, protein and enzyme activity reaching at a maximum at 6h, which was in part mediated through an increase in microsomal heme concentration. Heat shock protein 70 (HSP 70) was induced extremely rapidly, reaching at a maximum at 1 h, suggesting that HO-1 and HSP 70 gene expression are separately regulated. Inhibition of HO activity by tin mesoporphyrin (Sn-MP), which resulted in an increase in microsomal heme content, significantly exacerbated renal function as judged by the sustained increase in serum creatinine levels and extensive tubular epithelial cell injuries. In contrast, animals which did not receive Sn-MP showed normal creatinine levels and microsomal heme content 24 h after reperfusion, as well as restoration of abnormal renal histology.
Conclusion : These findings indicate that the expression of HO-1 in the ischemic kidney may be critical in the recovery of renal cell function in this animal model. These findings also suggest that HO-1 induction may play an important role in conferring protection on renal cells from oxidative damage caused by heme.
|
