The Research on the ion channels which are involved in the cytoprotective medianisms of endothelial cells in the atherosclerotic model animal

动脉粥样硬化模型动物内皮细胞保护中位作用离子通道的研究

• 批准号: 18590206
• 负责人: HAZAMA Akihiro
• 金额: $ 2.52万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590206/
• 关键词: atherosclerosis; Cl-channel; endothelial cells; amphotericin B; cvto-protection; ion channel; high NaC1 diet; Cl-channel blocker; 細胞障害; 塩素シオン; 塩素イオン

We established the primary culture of the endothelial cells from rabbits. We examined the role of ion channels in the cytoprotective effects. We applied amphotericin B on the endothelial cells which caused cell damage by the enhancement of the membrane permeability and tested different ionic conditions and ion channel blockers. We found that Cl- channel blockers, NPPB and DIDS, inhibited endothelial cell damage caused by amphotericin B. We also found that Cl- replacement by other organic anions suppressed cell-damage by amphotericin B. Cellular damage caused by hydrogen peroxide was also inhibited by Cl- channel blockers or Cl- free conditions. These results suggest that Cl- influx via Cl- channels might cause the endothelial cell damage during the formation of atherosclerosis. To access this question, we applied high NaC1 diet to the atherosclerosis model rabbit (KHC rabbit) for 6 months to check the formation of atherosclerosis. Surprisingly we found. that the formation of atherosclerosis was suppressed by the high NaC1 diet. We are investigating the mechanisms of this effect.

我们建立了兔内皮细胞的原代培养物。我们检查了离子通道在细胞保护作用中的作用。我们将两性霉素B应用于内皮细胞，通过增强膜通透性引起细胞损伤，并测试了不同的离子条件和离子通道阻滞剂。我们发现 Cl- 通道阻滞剂 NPPB 和 DIDS 可以抑制两性霉素 B 引起的内皮细胞损伤。我们还发现其他有机阴离子替代 Cl- 可以抑制两性霉素 B 引起的细胞损伤。过氧化氢引起的细胞损伤也可以被两性霉素 B 抑制。 Cl-通道阻滞剂或无 Cl-条件。这些结果表明，Cl-通过Cl-通道流入可能会在动脉粥样硬化形成过程中引起内皮细胞损伤。为了回答这个问题，我们对动脉粥样硬化模型兔（KHC兔）进行高NaC1饮食6个月，以检查动脉粥样硬化的形成情况。我们惊奇地发现。高NaC1饮食可抑制动脉粥样硬化的形成。我们正在研究这种效应的机制。

项目成果

Deep-sea water improves cardiovascular hemodynamics in Kurosawa and Kusanagi-Hypercholesterolemic (KHC) rabbits

• DOI: 10.1248/bpb.31.38
• 发表时间: 2008-01-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Katsuda, Shin-ichiro;Yasukawa, Takeshi;Hazama, Akihiro
• 通讯作者: Hazama, Akihiro