Huijberts M S, Wolffenbuttel B H, Crijns F R, Nieuwenhuijzen Kruseman A C, Bemelmans M H, Struijker Boudier H A
Department of Internal Medicine, University Hospital Maastricht, The Netherlands.
Diabetologia. 1994 Jan;37(1):10-4. doi: 10.1007/BF00428771.
Advanced glycation end-product-formation is thought to play a role in the development of diabetic angiopathy. By altering the structure of different extracellular matrix components advanced glycation end-products might affect vascular and glomerular permeability. In this study we investigated the effect of treatment with an inhibitor of advanced glycation end-product-formation, aminoguanidine, on vascular permeability and the development of albuminuria in streptozotocin-induced diabetic rats. Male Wistar Rp rats were randomized into a control group, a diabetic group, and an aminoguanidine-treated diabetic group. After 8 weeks, 24-h urine collections were taken and rats were implanted with an arterial and a venous catheter. mean arterial blood pressure was determined by intra-arterial measurement. Regional albumin clearances were assessed in the eye, ileum, lung, skeletal muscle and skin using an isotope technique. Mean arterial pressure in the diabetic group was significantly lower in the control and aminoguanidine-treated groups (p < 0.02). Regional albumin clearances were significantly increased in all tissues of diabetic rats compared to control rats (p < 0.05). Aminoguanidine treatment of diabetic rats resulted in a significant decrease of regional albumin clearance in all tissues except the lung (p < 0.05, lung p = 0.07). The development of albuminuria in diabetic rats however, was not affected by aminoguanidine.
晚期糖基化终产物的形成被认为在糖尿病性血管病的发展中起作用。通过改变不同细胞外基质成分的结构,晚期糖基化终产物可能会影响血管和肾小球的通透性。在本研究中,我们调查了用晚期糖基化终产物形成抑制剂氨基胍治疗对链脲佐菌素诱导的糖尿病大鼠血管通透性和蛋白尿发展的影响。雄性Wistar Rp大鼠被随机分为对照组、糖尿病组和氨基胍治疗的糖尿病组。8周后,收集24小时尿液,并给大鼠植入动脉和静脉导管。通过动脉内测量确定平均动脉血压。使用同位素技术评估眼睛、回肠、肺、骨骼肌和皮肤的局部白蛋白清除率。糖尿病组的平均动脉压在对照组和氨基胍治疗组中显著较低(p < 0.02)。与对照大鼠相比,糖尿病大鼠所有组织中的局部白蛋白清除率均显著增加(p < 0.05)。对糖尿病大鼠进行氨基胍治疗导致除肺以外的所有组织中的局部白蛋白清除率显著降低(p < 0.05,肺p = 0.07)。然而,糖尿病大鼠蛋白尿的发展不受氨基胍的影响。