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THE ROLE OF AGEs FORMATION OF KIDNEY IN THE PATHOGENESIS OF DIABETIC NEPHROPATHY

肾脏的年龄形成在糖尿病肾病发病机制中的作用

基本信息

批准号：
07671150
负责人：
NAKANO Koji
金额：
$ 1.22万
依托单位：
KYOTO PREFECTURAL UNIVERSITY OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671150/
关键词：
DIABETIC NEPHROPATHY SZ-DIABETIC RAT AGEs CROSSLINE Nitric Oxide Synthase COMPETITIVE ELISA DIABEIC COMPLICATIONS N-nitro-arginine (NNA)N-nitro-arginine (NNA)メイラード反応 AGE アマドリ生成物 C-NOS Competitive-ELISA Westen blot

项目摘要

To investigate the role of renal AGEs formation in the pathogenesis of diabetic nephropathy, I performed in vivo and in viro study using anti-crossline (XL) antibodies. XL is a isolated major in fluoresent advanced glycation end products (AGEs) (Ex/Em 379/463nm) resulting the reaction mixture ofepsilon-one lysine with D-glucose in vitro.(1) The role of AGEs formation and NO production in the pathogenesis of diabetic nephropathy : Urinary albumin excretion and renal XL formation of SZ diabetic rats were elevated significantly within 4 wks of SZ injection and continued to rise until the end of study. Urinary NO_3 (U-NO_3) and c-GMP excretion increased at 2 wks of SZ injection with the elevation of GFR.Administration of NO inhibitor, N-nitroarginine (NNA) to SZ-diabeic rats could suppress the elevated levels of GFR,RBF and U-NO_3. Moreover, administration of NNA suppressed anti C-NOS antibody staininng in cortical renal tissues. These results suggested that renal AGEs formation and NO production play a important role in the pathogenesis of diabetic nephropathy.(2) The measurement of XL in vivo speciments : We developed the competitive ELISA system to measure XL in biological specimens. The levels of XL in there serum, red blood cell membrane and tissue proteins in diabetic subjects were siginicatlly increased compared to those in non-diabetic ones. Mesurement of XL in biological specimens may provide an index of of the develpment of diabetic complications.

为了研究肾脏AGEs的形成在糖尿病肾病发病机制中的作用，我使用抗交叉线(XL)抗体进行了体内和体内研究。XL是荧光晚期糖基化终末产物(AGEs)(Ex/EM379/463 nm)中的一种分离主产物，它在体外由epsilon-one赖氨酸与D-葡萄糖反应生成。(1)AGEs的形成和NO的产生在糖尿病肾病的发病机制中的作用：SZ糖尿病大鼠在注射SZ后4周内尿白蛋白排泄量和肾脏XL的形成显著增加，并持续升高至研究结束。SZ-糖尿病大鼠注射SZ后2周尿NO_3(U-NO_3)和c-GMP排泄量随GFR升高而增加，给予NO抑制剂N-硝基精氨酸(NNA)可抑制GFR、RBF和U-NO_3的升高，并抑制肾皮质抗C-NOS抗体染色。这些结果提示肾脏AGEs的形成和NO的产生在糖尿病肾病的发病机制中起着重要作用。(2)体内XL的测定：我们建立了检测生物标本中XL的竞争性ELISA法。糖尿病患者血清、红细胞膜和组织蛋白中XL水平明显高于非糖尿病患者。生物标本中XL的检测可能为糖尿病并发症的发生发展提供一个指标。