The mechanism of inhibitory effect of AMP kinase for aldosterone-induced vascular damage

AMP激酶抑制醛固酮所致血管损伤的机制

• 批准号: 22590823
• 负责人: NAGATA Daisuke
• 金额: $ 2.5万
• 依托单位: Dokkyo Medical University (2011-2012)The University of Tokyo (2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590823/
• 关键词: 血管病態学; AMPキナーゼ; 血管内皮; アルドステロン; ミネラロコルチコイド; 一酸化窒素; 血管; 動脈硬化

We succeeded in creating vascular-endothelium-specific dominant-negative (dn) and constitutively-active (ca) AMPK transgenic mice using Tet-On expression system. In DOX-treated DOCA-salt TEK-rtTA/TRE-caAMPK mice, endothelium-dependent vasodilatation was significantly ameliorated compared to control DOCA-salt mice. L-NMMA pretreatment to inhibit eNOS completely canceled such ameliorating effect. Endothelium-dependent vasodilatation was significantly attenuated in DOX-treated DOCA-salt TEK-rtTA/TRE-dnAMPK mice thanin control mice. The blood pressure levels of three types DOCA-salt mice (Wt, caAMPK, dnAMPK) were not different, suggesting that such endothelial-protective effect of AMPK was BP-independent.

我们成功地利用Tet-On表达系统建立了血管内皮特异性显性阴性（dn）和组成活性（ca） AMPK转基因小鼠。在dox处理的doca盐TEK-rtTA/TRE-caAMPK小鼠中，与对照doca盐小鼠相比，内皮依赖性血管舒张得到显著改善。L-NMMA预处理抑制eNOS完全抵消了这种改善作用。dox处理的doca盐TEK-rtTA/TRE-dnAMPK小鼠的内皮依赖性血管舒张明显减弱。三种doca盐小鼠（Wt, caAMPK, dnAMPK）的血压水平没有差异，表明AMPK的内皮保护作用是不依赖于bp的。

项目成果

獨協医科大学 循環器・腎臓内科 長田研のホームページ

独协医科大学心脏病肾病科永田实验室主页

AMPキナーゼの血管保護作用の研究 -血管内皮特異的AMPK mutant transgenic miceを用いたin vivoでの検討

AMP激酶的血管保护作用研究——使用血管内皮特异性AMPK突变转基因小鼠进行体内研究

• 作者: Oba S;Kumano S;Suzuki E;Nishimatsu H;Takahashi M;Takamori H;Kasuya M;Ogawa Y;Sato K;Kimura K;Homma Y;Hirata Y;Fujita T.;Hirata Y;Sahara M;長田太助
• 通讯作者: 長田太助