Na^+/H^+ Exchange Plays a Role in Hypoxia-Reoxygenation induced ICAM-1 expression in CME

Na^ /H^ 交换在 CME 缺氧-复氧诱导的 ICAM-1 表达中发挥作用

• 批准号: 08671551
• 负责人: OTANI Hajime
• 金额: $ 1.22万
• 依托单位: Kansai 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: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671551/
• 关键词: reperfusion injury; Na^+; H^+ exchange; ICAM-1; CMEC; 心筋再潅流障害; ho-reflow現象

Na^+/H^+ exchange has been implicated in a mechanism for myocardial iscemia-reperfusion injury. Although cardiac myocytes have been a target for extensive resear.ch of this subject, little is known about a role of coronary microvascular endothelial cells (CMEC) in mvocardial reperfusion injury, Activation of Na^+/H^+ exchange and resultant intracellular Ca^<2+> ([Ca^<2+>]i) overload may stimulate intercellular adhesion molecule synthesis in CMEC whitch could paticipate in no reflow phenomenon. We have, therefore, investigated whether Na^+/H^+ exchange is involved in intercellular adhesion molecule-1 (ICAM-1) expression during reoxygenatlon in CMEC.The primary cultures of CMEC Isolated from adult rat hearts were subjected to simulated ischemia (hypoxic perfusion at pH6.4) for 45 minutes followed by reoxygenation at pH7.4. Dimethyl amirolide (DMA), an inhivitor of Na^+/H^+ exchanger, at a concentration of 0.1mM was added to perfusate during hypoxia and reoxygenation. The increase in [Ca^<2+>]i during hypoxia and reoxygenation was inhibited significantly (p<less than or equal>0.05) by the DMA treatment compared with the non-treatment cotrol. Northern blot analysis revealed enhanced expression of ICAM-1 m-RNA after 3 hours of reoxygenation, This was associated with immunocytochemically detected ICAM-1 protein expression which reached a maximum level at 8 hours after reoxygenation. Both ICAM-1 m-RNA and ICAM-1 protein expression were inhibited by DMA treatment. Conclusion : Na^+/H^+ exchange plays an essential role in [Ca^<2+>]i overload and ICAM-1 expression during reoxygenation in CMEC.

Na^+/H^+交换参与了心肌缺血-再灌注损伤的机制。尽管心肌细胞已成为广泛研究的靶resear.ch，但冠状动脉微血管内皮细胞（CMEC）在心肌缺血再灌注损伤中的作用尚不清楚。Na^+/H^+交换激活及由此引起的细胞内Ca^2+（[Ca^2+]i）超载可刺激CMEC合成细胞间粘附分子，从而参与无复流现象。因此，我们研究了Na^+/H^+交换是否参与了CMEC复氧过程中细胞间粘附分子-1（ICAM-1）的表达。在缺氧和复氧过程中，在灌流液中加入0.1mM的Na^+/H^+交换剂二甲基氨酰内酯（DMA）。与未处理对照相比，DMA处理显著抑制了缺氧和复氧期间[Ca^&lt;2+&gt;]i的增加（p <less than or equal>0.05）。北方印迹分析显示复氧后3 h ICAM-1 mRNA表达增强，与复氧后8h ICAM-1蛋白表达达到高峰有关。DMA处理可抑制ICAM-1 mRNA和ICAM-1蛋白表达。结论：Na^+/H^+交换在CMEC复氧过程中[Ca^2+]i超载和ICAM-1表达中起重要作用。