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.

项目成果

Hypertension promotes islet morphological changes with vascular injury on pre-diabetic status in SHRsp rats.

高血压促进 SHRsp 大鼠糖尿病前期状态的胰岛形态变化和血管损伤。

• DOI: 10.3109/10641963.2013.804539
• 发表时间: 2014
• 作者: Satoh M; Nagasu H; Haruna Y; Ihoriya C; Kadoya H; Sasaki T; Kashihara N.
• 通讯作者: Kashihara N.

T Type Ca-Channel Blocker Exerts Anti-Albuminuic Effect through Amelioration of eNOS Uncoupling in Hypertensive Kidney Disease Model

T 型 Ca 通道阻滞剂通过改善高血压肾病模型中的 eNOS 解偶联发挥抗白蛋白作用

• 发表时间: 2013
• 作者: Itano S; Kidokoro K; Satoh M; Sasaki T; Kashihara N
• 通讯作者: Kashihara N

Development of Novel Technique to Visualize in vivo Renin Activity and Analysis of Reno-Protective Actions of Renin Inhibitor in Diabetic Nephropathy

体内肾素活性可视化新技术的开发及肾素抑制剂对糖尿病肾病的肾病保护作用分析

• 发表时间: 2013
• 作者: Kidokoro K; Satoh M; Nishi Y; Ihoriya C; Kadoya H; Komai N; Sasaki 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

Maintenance of endothelial guanosine triphosphate cyclohydrolase I ameliorates diabetic nephropathy

维持内皮鸟苷三磷酸环水解酶 I 可改善糖尿病肾病

• DOI: 10.1681/asn.2012080783
• 发表时间: 2013
• 影响因子: 13.6
• 作者: Kidokoro K; Satoh M; Channon KM; Yada T; Sasaki T; Kashihara N
• 通讯作者: Kashihara N