项目名称: 生理和缺血再灌注状态下的冠脉内皮功能 - - 内皮离子通道间信号关联的研究
项目编号: No.81200123
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 医学一处
项目作者: 杨沁
作者单位: 香港中文大学深圳研究院
项目金额: 23万元
中文摘要: 内皮细胞释放血管活性物质调节血管张力。中小电导钙激活钾通道(IKCa和SKCa)的激活是内皮源性超极化因子EDHF的作用机制,而内皮细胞内Ca2+浓度升高是通道激活的先决条件。规范瞬时受体电位通道TRPC在内皮Ca2+调节中起重要作用。然而TRPC是否与KCa关联参与内皮功能未见报道。本研究将首先明确TRPC3在内皮KCa活性及在KCa依赖性EDHF功能中的作用。TRPC3和KCa是否存在物理联系也将被研究。缺血再灌注/缺氧再复氧(H-R)时内皮功能失调。我们发现H-R时EDHF损伤是由于内皮IKCa和SKCa的抑制。我们也证实H-R可抑制TRPC3而致内皮Ca2+信号障碍。然H-R时TRPC3抑制会否导致内皮KCa及KCa依赖性EDHF功能抑制尚不明确。本项目通过对内皮离子通道关联的研究可为EDHF信号串联和H-R时内皮功能失调提供新信息,有助于发现新的靶点防治缺血缺氧时的内皮功能障碍。
中文关键词: 内皮舒张因子;冠脉循环;离子通道;缺血再灌注损伤;
英文摘要: Endothelial cells release vasoactive agents to regulate vascular tone. The normal function of endothelium is controlled by a number of ion channels that include calcium-activated potassium channels of intermediate- and small- conductance (IKCa and SKCa). Previous studies have demonstrated that the activation of endothelial IKCa and SKCa underlies the action of endothelium-derived hyperpolarizing factor (EDHF) that requires a rise of intracellular Ca2+ concentration ([Ca2+]i). Canonical transient receptor potential channels (TRPC) are Ca2+-permeable channels that are important in endothelial Ca2+ regulation. However, it remains unknown whether TRPC channels may associate with KCa channels in endothelial function. In this study, we will first investigate the role of TRPC3 in the channel activity of endothelial KCa and the role of TRPC3 channel in endothelial KCa channel-dependent EDHF-responses. Whether the functional association between TRPC3 and KCa involves physical interactions will be further studied. Endothelial dysfunction occurs during ischemia-reperfusion (I-R) / hypoxia-reoxygenation (H-R) injury. Our previous studies have demonstrated that the impairment of EDHF-type responses in coronary arteries under H-R conditions is attributable to the inhibition of channel activity of IKCa and SKCa in endot
英文关键词: endothelium-derived relaxing factors;coronary circulation;ion channels;ischemia-reperfusion injury;