Reduction of the accumulation of advanced glycation end products by ACE inhibition in experimental diabetic nephropathy
Reduction of the accumulation of advanced glycation end products by ACE inhibition in experimental diabetic nephropathy
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DOI：
10.2337/diabetes.51.11.3274
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发表时间：
2002-11-01
期刊：
影响因子：
7.7
通讯作者：
Osicka, TM
中科院分区：
文献类型：
--
作者：
Forbes, JM;Cooper, ME;Osicka, TM
探讨ACE抑制剂对晚期糖基化终产物（AGES）形成和氧化应激的影响。将链脲佐菌素诱导的糖尿病动物随机分为无治疗组、ACE抑制剂雷米普利（3 mg/l）组或AGE形成抑制剂氨基胍（1 g/l）组，并随访12周。同时随访对照组。肾AGE积累，通过免疫组织化学和血清和肾脏荧光测定，糖尿病动物增加。这是衰减的两个ramieside和氨基胍到类似的程度。蛋白质氧化的标志物硝基酪氨酸也遵循类似的模式。AGES受体、膜结合NADPH氧化酶亚基gp 91 phox和核转录因子-kappaB的基因表达均因糖尿病而增加，但不受任何治疗方案的影响。另外两种AGE受体AGE R2和AGE R3在研究期间保持不变。本研究已经确定了实验性糖尿病肾病中血管紧张素系统与AGES积累之间的关系，这可能与氧化应激有关。
The effect of ACE inhibition on the formation of advanced glycation end products (AGES) and oxidative stress was explored. Streptozocin-induced diabetic animals were randomized to no treatment, the ACE inhibitor ramipril (3 mg/l), or the AGE formation inhibitor aminoguanidine (1 g/l) and followed for 12 weeks. Control groups were followed concurrently. Renal AGE accumulation, as determined by immunohistochemistry and both serum and renal fluorescence, were increased in diabetic animals. This was attenuated by both ramipril and aminoguanidine to a similar degree. Nitrotyrosine, a marker of protein oxidation, also followed a similar pattern. The receptor for AGES, gene expression of the membrane-bound NADPH oxidase subunit gp91phox, and nuclear transcription factor-kappaB were all increased by diabetes but remained unaffected by either treatment regimen. Two other AGE receptors, AGE R2 and AGE R3, remained unchanged for the duration of the study. The present study has identified a relationship between the renin-angiotensin system and the accumulation of AGES in experimental diabetic nephropathy that may be linked through oxidative stress.