Development of New Experimental Model of Diabetic Microvascular Disease: Experimental Animal and in vitro Model.

糖尿病微血管疾病新实验模型的开发：实验动物和体外模型。

• 批准号: 62870047
• 负责人: KANAZAWA Yasunori
• 金额: $ 16.7万
• 依托单位: Omiya Medical Center, Jichi Medical School (1988-1989)The University of Tokyo (1987)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62870047/
• 关键词: Diabetic microangiopathy; SHR; Streptozotocin diabetes; Diabetic nephropathy; Basement membrane thickness; Irregularity of vascular diameter; Mesangial tissue; メザンギウム; SHR(自然発症高血圧ラット); ストレプトゾトシン糖尿病; 糖尿病性細小血管; ストレプトゾトシン糖尿; 血管内皮細胞ニフエジピン; Wister

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 … More 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

本研究旨在建立一种新的糖尿病微血管病变的实验模型。糖尿病并发症尤其是肾脏疾病研究进展缓慢的主要原因是难以找到与长期糖尿病患者肾脏形态学变化相似的动物模型。表现为基底膜不规则增厚、小血管管径不规则、小血管外细胞（肾小球系膜细胞）变性。在功能上，增加蛋白质排泄。肾小球滤过率升高是早期变化的主要观察指标。本研究是在糖尿病代谢变化和高血压应激（或损伤）将在短时间内以可重复的方式再现这些变化的假设下开始的。我们用扫描电子显微镜分析了 ...更多信息 尾静脉注射链脲佐菌素30 ~ 35 mg/kg，可使糖尿病大鼠产生轻、中度糖尿病，并可将糖尿病大鼠的糖尿病控制在非酮症水平。这种情况有点类似于人类糖尿病中的NIDDM。糖尿病3个月后，自发性高血压大鼠（SHR）的肾小球毛细血管基底膜出现不规则增厚。肾小球毛细血管直径不规则增厚。这些也可以在电子显微镜下观察到。功能分析显示糖尿病SHR肾小球滤过率增加，尿蛋白排泄量增加.这些变化与人类糖尿病早期肾脏病变中观察到的变化完全相同，重复实验表明这些变化具有可重复性。因此，该模型是研究糖尿病微血管病变的良好模型。我们的硝苯地平实验表明，形态学变化的改善与血压的降低平行，这也表明我们的假设的有效性。少

项目成果

金澤康徳: "SHRを用いた糖尿病性細小血管症モデルの作製" 糖尿病動物. 1. 233-238 (1987)

Yasunori Kanazawa：“利用 SHR 制备糖尿病微血管病模型”糖尿病动物。1. 233-238 (1987)