Elucidation of molecular mechanisms and therapeutic strategies for diabetic angiopathic complications

阐明糖尿病血管病变并发症的分子机制和治疗策略

基本信息

批准号：
17591074
负责人：
TSUKAHARA Hirokazu
金额：
$ 2.37万
依托单位：
University of Fukui
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Angiopathy is a major chronic complication of diabetic mellitus and an important cause of increased morbidity and mortality among the patients with diabetes. Possible mechanisms of untoward effects of hyperglycemia include high oxidative stress status. Loads of reactive oxygen species (ROS) that overburden antioxidant systems induce oxidative stress in the body. Major cellular targets of ROS are membrane lipids, proteins, nucleic acids, and carbohydrates. Other investigators and I have introduced specific biomarkers for oxidative damages and antioxidant defenses into the field of pediatric medicine. Specifically, I have presented age-related reference normal ranges of oxidative stress biomarkers, including urinary acrolein-lysine, 8-hydroxy-2'-deoxyguanosine, nitrite/nitrate, and pentosidine, and the changes of the parameters in diabetes mellitus. I have also presented the data indicating that expression of both adhesion molecules and chemokines in human microvascular endothelial cells induced by inflammatory cytokine TNF-α is inhibited significantly by pretreatment with antioxidants or NO donors, possibly in part through blocking the activation of NF-κB. These experimental results suggest a potential therapeutic approach using antioxidants or NO donors in the treatment of oxidative stress related inflammatory diseases. These informations will be helpful to understand the pathogenesis and management of diabetic angiopathy, including atherosclerosis, retinopathy and nephropathy.

血管病是糖尿病性麦芽菌的主要慢性并发症，也是糖尿病患者发病率和死亡率增加的重要原因。高血糖不良影响的可能机制包括高氧化物应激状态。过度抗氧化剂系统诱导体内氧化物应激的活性氧（ROS）的负载。 ROS的主要细胞靶标是膜脂质，蛋白质，核酸和碳水合物。我和其他研究人员已将特定的生物标志物引入了儿科医学领域的氧化损害和抗氧化剂防御。我已经提出了与年龄相关的参考氧化应激生物标志物的常规参考范围，包括尿丙烯蛋白赖氨酸，8-羟基-2'-脱氧鸟苷，硝酸盐/硝酸盐和五肽酸酯，以及糖尿病中参数的变化。我还介绍了数据表明，炎性细胞因子TNF-α诱导的人类微血管内皮细胞中粘附分子和趋化因子的表达显着抑制，通过用抗氧化剂预处理或没有供体，可以通过阻断NF-κB的激活来部分地在部分中通过阻断NF-κB的激活来抑制。这些实验结果表明，使用抗氧化剂或没有供体治疗氧化应激相关炎症性疾病的潜在治疗方法。这些信息将有助于了解糖尿病血管病的发病机理和管理，包括动脉粥样硬化，视网膜病和肾病。