Elucidation of the molecular basis attributed to onset of abnormal retinal hemodynamics and strategy of novel prevention drugs for retinopathy

阐明视网膜血流动力学异常发生的分子基础以及新型视网膜病变预防药物的策略

• 批准号: 21590102
• 负责人: ISHII Kunio
• 金额: $ 2.91万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590102/
• 关键词: 薬理学; 微小循環; 糖尿病; 血管生物学; 網膜

This study demonstrated that retinal vasodilator responses mediated through the mechanism involving activation of the large-conductance Ca^<2+>-activated K^+(BK_<Ca>) channel was diminished at the early stage of diabetes in rats. Furthermore, it was suggested that the oxydative stress was increased in retinal blood vessels of diabetes rats. Thus, impairment of BK_<Ca> channel function and increased oxidative stress may contribute to abnormal retinal hemodynamics in diabetes and consequently play an important role in the pathogenesis of diabetic retinopathy. In conclusion, drugs that improve retinal circulation and possess antioxidative effect are considered to be novel candidates for prevention of retinopathy.

本研究表明，在糖尿病大鼠早期，通过大电导Ca^<2+>-激活的K^+(BK_<Ca>)通道激活介导的视网膜血管扩张反应减弱。此外，糖尿病大鼠视网膜血管氧化应激增加。因此，BK_<Ca>通道功能的损害和氧化应激的增加可能导致糖尿病视网膜血流动力学异常，从而在糖尿病视网膜病变的发病机制中起重要作用。总之，改善视网膜循环和具有抗氧化作用的药物被认为是预防视网膜病变的新候选药物。

项目成果

Hyperglycemia Impairs Acetylcholine-Induced Vasodilation of Retinal Arterioles Through Polyol Pathway-Independent Mechanisms in Rats

• DOI: 10.1254/jphs.09312fp
• 发表时间: 2010-03-01
• 期刊: JOURNAL OF PHARMACOLOGICAL SCIENCES
• 影响因子: 3.5
• 作者: Mori, Asami;Saigo, Orie;Ishii, Kunio
• 通讯作者: Ishii, Kunio

Noradrenaline contracts rat retinal arterioles via stimulation of α_<1A>- and (α_<1D>-adrenoceptors

去甲肾上腺素通过刺激α_<1A>-和(α_<1D>-肾上腺素受体)收缩大鼠视网膜小动脉

• DOI: 10.1016/j.ejphar.2011.10.012
• 发表时间: 2011
• 期刊: Eur J Pharmacol
• 影响因子: 5
• 作者: Mori A;Hanada M;Sakamoto K;Nakahara T;Ishii K
• 通讯作者: Ishii K

Pharmacological evidence for the presence of functional ss_3-adrenoceptors in rat retinal blood vessels

大鼠视网膜血管中存在功能性 ss_3-肾上腺素受体的药理学证据

• 发表时间: 2010
• 期刊: Naunyn Schmiedebergs Arch Pharmacol
• 作者: Mori A;Miwa T;Sakamoto K;Nakahara T;Ishii K
• 通讯作者: Ishii K

Drugs for improving retinal circulation : Current status and future.

改善视网膜循环的药物：现状和未来。

• 发表时间: 2010
• 作者: Ishii K;Mori A;Sakamoto Nakahara T.
• 通讯作者: Sakamoto Nakahara T.

新規網膜血流量測定システムの構築とそれによる網膜循環改善薬の探索

新型视网膜血流测量系统的构建及利用该系统寻找改善视网膜循环的药物

• 发表时间: 2011
• 作者: 森麻美;花田真幸;坂本謙司;中原努;石井邦雄
• 通讯作者: 石井邦雄