Development of intravital microscope for measurement of capillary and coronary blood flow, and coronary microvascular disturbance of diabetes mellitus and circulatory reconstruction

开发用于测量毛细血管和冠状动脉血流量、糖尿病冠状动脉微血管紊乱和循环重建的活体显微镜

• 批准号: 19300167
• 负责人: YADA Toyotaka
• 金额: $ 8.49万
• 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 (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19300167/
• 关键词: 医用; 生体画像; 糖尿病; 冠微小循環障害; 急性心筋梗塞; 内皮由来過分極因子; 過酸化水素; 一酸化窒素; 内皮由来弛緩因子; 側副血行路; 生体顕微鏡; 毛細血管; 血管内皮機能; CCD生体顕微鏡

It was possible to visualize the blood capillary and observe the coronary microcirculation in dogs of diabetes mellitus by a CCD intravital microscope of high accuracy. We have demonstrated that endothelium-derived hyperpolarizing factors (EDHF)/H_2O_2 and NO were key mediators of vasodilatation of coronary native collateral microvassels after myocardial ischemia, and erythropoietin (EPO) and angiotensin receptor blockers (ARB) enhanced the vasodilatation in canine coronary collateral microvessels in vivo, and also enhanced H_2O_2-induced canine coronary collateral vasodilatation. Myocardial expression of eNOS and Akt activity as the ratio of phospho-Akt/total Akt in the myocardium of ischemic LAD area of control group were increased by EPO. These results indicate that EPO improves eNOS protein expression and Akt phosphorylation, at least in part, through activation of PI3K/Akt and EDHF/H_2O_2 pathway. EPO, ARB and EDHF/H_2O_2 play an important role for improvement factor of vascular endothelial disturbance.

可以通过高准确性的CCD插入式显微镜观察到血液毛细血管并观察糖尿病犬狗的冠状动脉微循环。 We have demonstrated that endothelium-derived hyperpolarizing factors (EDHF)/H_2O_2 and NO were key mediators of vasodilatation of coronary native collat​​eral microvassels after myocardial ischemia, and erythropoietin (EPO) and angiotensin receptor blockers (ARB) enhanced the vasodilatation in canine coronary collat​​eral microvessels in vivo, and还增强了H_2O_2诱导的犬冠状动脉副血管舒张。 EPO增加了eNOS和AKT活性的心肌表达，作为缺血性LAD面积的磷酸化/总AKT的比率。这些结果表明，EPO至少通过激活PI3K/AKT和EDHF/H_2O_2途径来改善ENOS蛋白表达和Akt磷酸化。 EPO，ARB和EDHF/H_2O_2在提高血管内皮障碍的改善因素方面起着重要作用。

项目成果

Crucial role of Cu/Zn-SOD in the synthesis of endothelium-derived hyperpolarizing factor(EDHF)during reactive hyperemia in mouse mesenteric microcirculation in vivo

Cu/Zn-SOD在小鼠肠系膜微循环反应性充血期间内皮源性超极化因子（EDHF）合成中的关键作用

• 发表时间: 2007
• 作者: Wang W;et al;Toyotaka Yada
• 通讯作者: Toyotaka Yada

Protective role of hydrogen peroxide and erythropoietin during acute coronary occlusion/reperfusion in native coronary collateral circulation in dogs in vivo、Circulation

过氧化氢和促红细胞生成素在犬体内急性冠状动脉闭塞/再灌注过程中对天然冠状动脉侧支循环的保护作用，循环

• 发表时间: 2007
• 作者: Toyotaka Yada;Hiroaki Shimokawa;Osamu Hiramatsu;Yoshiro Shinozaki;Hidezo Mori;Masami Goto;Yasuo Ogasawara;Fumihiko Kajiya
• 通讯作者: Fumihiko Kajiya

ole of Cu, Zn-SOD in the synthesis of endogenous vasodilator hydrogen peroxide during reactive hyperemia in mouse mesenteric microcirculation in vivo

Cu、Zn-SOD在体内小鼠肠系膜微循环反应性充血过程中内源性血管扩张剂过氧化氢合成中的作用

• 发表时间: 2008
• 期刊: Am J Physiol Heart Circ Physiol Vol.294,No.1
• 作者: Toyotaka Yada;Hiroaki Shimokawa;Keiko Morikawa;以下省略(6名)
• 通讯作者: 以下省略(6名)

Role of H2O2 as an endogenous EDHF during coronary occlusion and injection of erythropoietin in canine coronary native collateral microvessels、Circulation Journal

H2O2 在冠状动脉闭塞期间作为内源性 EDHF 的作用以及在犬冠状动脉天然侧支微血管中注射促红细胞生成素，《循环杂志》

• 发表时间: 2009
• 作者: Toyotaka Yada;Hiroaki Shimokawa;Osamu Hiramatsu;Yoshiro Shinozaki;Hidezo Mori;Masami Goto;Yasuo Ogasawara;Fumihiko Kajiya
• 通讯作者: Fumihiko Kajiya

Crucial role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice、Circulation

一氧化氮合酶系统在小鼠内皮依赖性超极化中的关键作用，循环

• 发表时间: 2008
• 作者: Aya Takaki;Keiko Morikawa;Yoshinori Murayama;Ender Tekes;Hiroto Yamagishi;Junko Ohashi;Masato Tsutsui;Toyotaka Yada;Nobuyuki Yanagihara;Hiroaki Shimokawa
• 通讯作者: Hiroaki Shimokawa