2002 Fiscal Year Final Research Report Summary
Study on the effect of loss of renal functioning mass on remaining kidney in Streptozotocin-induced diabetic rats
| Project/Area Number |
12671561
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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 |
Urology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
ITO Fumio Tokyo Women's Medical University, Department of Urology, clinical fellow, 医学部, 助手 (20211683)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Yasunobu Tokyo Women's Medical University, Department of Urology, clinical fellow, 医学部, 助手 (70307594)
OKUDA Hisashi Tokyo Women's Medical University, Department of Urology, clinical fellow, 医学部, 助手 (80246545)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Nephrectomy / Diabetic nephropathy / Streptozotocin |
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| Research Abstract |
In this study, we evaluated the combined effect of loss of renal functioning mass and hyperglycemia on the remnant kidney using streptozotocin (STZ)-induced rats. Diabetes was confirmed and surgical preparation was performed one week after STZ injection. Diabetic rats were divided into four groups : group 1, laparotomy alone ; group 2, heminephrectomy of one side ; group 3, complete nephrectomy of one side ; group 4, complete nephrectomy of one side and heminephrectomy of another side. Age-matched normal rats were also served as controls. Physical parameters were measured and blood, urine and tissue samples were collected at 7 day-intervals during 4-week experimental period. Creatinine clearance (CCr) was calculated using blood and urine samples. Quantitative RT-PCR analysis of TGF-β1, collagen IV and fibronectin, morphological analysis of the interstitial volume, and immunohistochemistory for AGEs were performed using tissue samples. Gain of body weight was inhibited comparing to that of non-diabetic groups. Gain of wet weight of kidneys in diabetic rats was steeper than in non-diabetic rats. Diabetic rats had an apparent increase in CCr. However, it had tendency to decline in diabetic rats with maximal loss of renal mass, which was correlated to TGF-β1 expression. It is suggested that sudden change of local circumstances due to loss of renal volume increase local angiotensin II level followed by up-regulation of TGF-β1. AGEs, another potent stimulator of TGF-β1, had been already detected since an early period in all diabetic rats. As downstream phenomenon possibly led by TGF-β1, an increase in extracellular fibers or up-regulation of collagen and fibronection was not confirmed. In conclusion, diabetes and loss of renal mass has an adverse effect on the remaining kidney synergistically if the loss volume exceeds 50% of a whole volume even in the early stage of diabetic nephropathy.
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Research Products
(1 results)
