Investigation of pathogenesis of albuminuria in chronic kidney disease and its association with cardiovascular complications

慢性肾脏病白蛋白尿发病机制及其与心血管并发症的关系研究

• 批准号: 23591209
• 负责人: KOMAI Norio
• 金额: $ 3.41万
• 依托单位: Kawasaki Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591209/
• 关键词: アルブミン尿; 内皮障害; 一酸化窒素; 慢性腎臓病; 酸化ストレス; 活性酸素種; 内皮細胞; 糸球体; 血管透過性

Albuminuria is an independent risk marker for development of cardiovascular disease. We hypothesized that albuminuria could be caused by glomerular endothelial injuries/dysfunctions. We have successfully developed the novel in vivo-imaging technique by which we can visualize microcirculation and filtration status by using 2-phton lasermicroscopy. We found that in diabetes, endothelial nitric oxide synthase (eNOS) produces superoxide anion rather than nitric oxide, referred to as "eNOS uncoupling," which contributes to endothelial dysfunction, albuminuria, and diabetic nephropathy. Reduced levels of endothelium-derived tetrahydrobiopterin (BH4), an essential cofactor for eNOS, promote eNOS uncoupling. We also demonstrated that renin-angiotensin system is deeply associated with generation of oxidative stress through activation of NADPH-oxidase. We have elucidated that maintenance of endothelial integrity ameliorates diabetic nephropathy.

白蛋白尿是心血管疾病发展的独立危险标志物。我们假设蛋白尿可能是由肾小球内皮损伤/功能障碍引起的。我们已经成功地开发了新的在体成像技术，我们可以通过使用2光子激光显微镜可视化微循环和过滤状态。 我们发现，在糖尿病中，内皮型一氧化氮合酶（eNOS）产生超氧阴离子而不是一氧化氮，称为“eNOS解偶联”，这有助于内皮功能障碍，蛋白尿和糖尿病肾病。内皮衍生的四氢生物蝶呤（BH 4），eNOS的一个重要的辅因子，水平降低，促进eNOS解偶联。我们还证明，肾素-血管紧张素系统是通过激活NADPH氧化酶与氧化应激的产生密切相关。我们已经阐明，维持内皮完整性可改善糖尿病肾病。

项目成果

Preservation of Endothelial GTP Cyclohydrolase I Activity and Improvement of Renal Nitric Oxide Availability Prevent the Development of Diabetic Nephropathy

保护内皮 GTP 环化水解酶 I 活性并提高肾一氧化氮可用性可预防糖尿病肾病的发生

• 发表时间: 2012
• 作者: Kidokoro K,Satoh M,Nagasu H;Nishi Y;Ihoriya C;Kadoya H;Yada T,keith M Channon,Sasaki T,Kashihara N
• 通讯作者: Yada T,keith M Channon,Sasaki T,Kashihara N

Preservation of Endothelial GTP Cyclohydrolase I Activity and Improvement of Renal Nitric Oxide Availability Prevent the Development of Albuminuria in Diabetes.

保护内皮 GTP 环化水解酶 I 活性和改善肾一氧化氮可用性可预防糖尿病患者出现白蛋白尿。

• 发表时间: 2012
• 作者: Kidokoro K;Satoh M;Yada T;Kashihara N.
• 通讯作者: Kashihara N.

Endothelial Dysfunction promotes the Transition from Compensatory Renal Hypertrophy to Kidney Injury after Unilateral Neophrectomy in Mice

内皮功能障碍促进小鼠单侧肾切除术后代偿性肾肥大向肾损伤的转变

• 发表时间: 2012
• 作者: Kadoya H,Nagasu H,Satoh M,Sasaki T;Kashihara N
• 通讯作者: Kashihara N

Implications of Oxidative Stress Derived from Endothelial NAD(P) H Oxdase in the Development of Diabetic Nephropathy

内皮 NAD(P) H 氧化酶产生的氧化应激在糖尿病肾病发展中的意义

• 发表时间: 2011
• 作者: Nagasu;H;Satoh;M;Kuwabara;A;Kidokoro;K;Tomita;N;Sasaki;T;Kashihara;N
• 通讯作者: N

Stimulation of Soluble Guanylate Cyclase Attenuates Epithelial-Mesenchymal Transition of the Peritoneal Membrane and Prevent the Development of Peritoneal Fibrosis.

刺激可溶性鸟苷酸环化酶可减弱腹膜上皮-间质转化并防止腹膜纤维化的发展。

• 发表时间: 2012
• 作者: Kadoya H;Satoh M;Nagasu H;Kidokoro K;Kashihara N;et al
• 通讯作者: et al