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Mechanism of myocardial tissue damage in patients with diabetes, chronic renal failure and hemodialysis

糖尿病、慢性肾功能衰竭及血液透析患者心肌组织损伤机制

基本信息

批准号：
14570171
负责人：
SAKATA Noriyuki
金额：
$ 2.18万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570171/
关键词：
Chronic renal failure Diabetes mellitus Myocardial tissue Myofilament Glycoxidation Hydroxyl radical

项目摘要

The present study was done to clanfy the role of glycoxidation stress on the damage of cardiac muscle and arterial tissue in patients with diabetes, chronic renal failure and hemodialysis. The level of pentosidine, a glycoxidation product, was significantly increased in the matrix proteins of arterial tissues and myofilament protein of myocardium of the patients with hemodialysis and chronic renal failure as compared to controls. The calcium-binding activity arid pentosidine level of collagen, a matrix protein, was time-dependently increased with in vitro incubation of glucose. In arterial tissues, the glycoxidative modification of matrix protein may be closely related to medial calcification in patients with diabetes and chronic renal failure. The level of urea hydrogen peroxide (UHP) was significantly higher in cardiac tissues of patients with chronic renal failure and hemodialysis than in those of controls. In vitro incubation of cardiac tissues with ribose formed pentosidine in dose dependent manner of urea or serum ultrafiltrate of patients with hemodialysis. The presence of urea, dose-dependently increased the generation of UHP in these incubation systems. Blocking experiment with catalase, SOD and mannitol showed that pentosidine formation was significantly enhanced by hydroxyl radical generated from UHP via Fenton reaction. Thus, glycoxidative modification of these proteins may be enhanced by the formation of UHP via Fenton reaction and may contribute to cardiac and arterial dysfunction in patients with chronic renal failure and hemodialysis.

本研究旨在探讨糖氧化应激在糖尿病、慢性肾功能衰竭和血液透析患者心肌和动脉组织损伤中的作用。与对照组相比，血液透析和慢性肾功能衰竭患者动脉组织基质蛋白和心肌肌丝蛋白中的糖氧化产物戊糖苷水平显著升高。钙结合活性和戊糖水平的胶原蛋白，基质蛋白，在体外培养的葡萄糖与时间依赖性增加。在动脉组织中，基质蛋白的糖氧化修饰可能与糖尿病和慢性肾功能衰竭患者的中膜钙化密切相关。慢性肾功能衰竭血液透析患者心肌组织中过氧化氢尿素（UHP）水平显著高于对照组。心肌组织与核糖体外孵育形成的戊糖苷与尿素或血液透析患者血清超滤液呈剂量依赖性。尿素的存在下，剂量依赖性地增加在这些孵育系统中的UHP的产生。过氧化氢酶、超氧化物歧化酶和甘露醇的阻断实验表明，超高压通过芬顿反应产生的羟自由基能显著促进戊糖苷的形成。因此，这些蛋白质的糖氧化修饰可能通过芬顿反应形成UHP而增强，并可能导致慢性肾功能衰竭和血液透析患者的心脏和动脉功能障碍。