1989 Fiscal Year Final Research Report Summary
Development of New Experimental Model of Diabetic Microvascular Disease: Experimental Animal and in vitro Model.
| Project/Area Number |
62870047
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Omiya Medical Center, Jichi Medical School (1988-1989)
The University of Tokyo (1987) |
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Principal Investigator |
KANAZAWA Yasunori Jichi Medical School Professor, 医学部, 教授 (10010399)
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| Co-Investigator(Kenkyū-buntansha) |
NODA Mitsuhiko 東京大学, 医学部附属病院, 医員
OKA Yoshitomo University of Tokyo, Faculty of Med. Assistant, 医学部, 助手 (70175256)
KOMEDA Kajuro Tokyo Medical College Assist. Prof., 実験動物センター, 助教授 (90074533)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Diabetic microangiopathy / SHR / Streptozotocin diabetes / Diabetic nephropathy / Basement membrane thickness / Irregularity of vascular diameter / Mesangial tissue / メザンギウム |
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| Research Abstract |
The Research had been started to develop a new experimental model to study diabetic micro-vascular diseases. The major reason of the retardation of the research of diabetic complication especially kidney diseases was in the difficulty to find out animal model exhibiting almost comparable morphological changes which could be observed in long standing diabetic patients' kidney. These are irregular basement membrane thickening, irregular diameter of small vessels and external cells of small vessels ( mesangial cells of glometular tufts ) denaturation. Functionally, increase of protein excretion..and elevated glomerular filtration rate are the major observation of early changes. We had not been able to obtain model(s) that had these conditions.
The investigation was started under the hypothesis that diabetic metabolic changes and hypertensive stress (or damage) will reproduce these changes in short period of time and reproducible fashion. We used scanning electron microscope to analyze the
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vascular structural changes, this method was a good supplementation of other morphological methods.
Thirty to 35 mg/kg of streptozotocin injection from tail vein produced mild and medium grade diabetes, which can be well controlled in the level of non-ketotic state. This condition is somewhat similar to those of NIDDM in human diabetes. After 3 months of diabetes, spontaneously hypertensive rats (SHR) produced irregular basement membrane thickening in their glomerular capillary. The diameter of glomerular capillary of these animals were irregularly thickened. These could be observed also electron-microscope. The functional analysis disclosed diabetic SHR showed incteasedglomerular filtration rate and elevated urinary protein excretion. These are exactly the same to those observed in early nephropathic changes in human diabetes.
Repeated experiments indicate the reproducibility of these changes. Thus we conclude that this diabetic SHR model is a good model to study diabetic microangiopathy. Our nifedipine experiment which showed amerioration of morphological changes in parallel with decrease of blood pressure suggest also validity of our hypothesis. Less
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