| Project/Area Number |
17500343
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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 |
Rehabilitation science/Welfare engineering
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
KANAZAWA Masayuki Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (60282050)
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| Co-Investigator(Kenkyū-buntansha) |
KOHZUKI Masahiro Tohoku University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (70234698)
MINAMI Naoyoshi Hospital, Lecturer, 病院・講師 (80333821)
ITO Osamu Tohoku University, Graduate School of Medicine, Research Associate, 大学院医学系研究科, 助手 (00361072)
SATO Toshincbui Hospital, Associate Professor, 病院・助教授 (50312583)
TAKAGI Michiaki Yamagata University Hospital, Associate Professor, 医学部附属病院, 助教授 (40241707)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | diabetic nephropathy / chronic exercise / losartan / rat / index of glomerular sclerosis / relative interstitial volume / immunohistochemistry / endurance / 骨格筋毛細血管 |
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| Research Abstract |
To assess the renal effects of chronic exercise (EX) in a rat model of diabetic nephropathy (DN) and the benefits of combined EX and angiotensin II type-1 receptor antagonist, losartan (LOS).
Heminephrectomized Goto-Kakizaki rats were fed a high-caloric diet and had free access to 30% sucrose solution to develop DN. The rats were divided into 4 groups: 1) no EX (C); 2) EX with treadmill running (20m/min, 60min/day, 5days/week); 3) LOS(5mg/kg/day); 4) EX+LOS, and the rats were treated for 12 weeks. At the end of the experiment, remnant kidneys were removed, and were analyzed for histopathology, and for immunohistologically using antibodies against ED-1, alpha-smooth muscle actin (SMA) and Wilms' tumor (WT)-1.
Systolic blood pressure (SBP) in the LOS and EX+LOS groups was significantly lower than that in the C and EX groups. EX, EX+LOS and LOS blunted increases in proteinuria. The index of glomerular sclerosis (IGS) and the relative interstitial volume of the renal cortex were significantly improved in the EX, EX+LOS and LOS groups than those in the C group. Particularly, the IGS, the expressions of ED-1 and alpha-SMA in the glomerulus were the lowest, and the number of WT-1 positive cells was the highest in the EX+LOS group. The ability of endurance running in the EX and EX+LOS groups was significantly stronger than that in the LOS and C groups.
These results suggested that EX and LOS have renoprotective effects, and that the effects of EX were not related to the SBP reduction. These results also suggested that the simultaneous treatment with EX and LOS provided greater renoprotective effect than that of LOS alone and may affect the macrophage infiltration, the mesangial activation, and the podocyte loss in this rat model of DN. They also suggested that EX has the effect which enhances endurance without renal complications in this rat model.
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