Myocardial preconditioning and remote renal preconditioning -: Identifying a protective factor using proteomic methods?
Myocardial preconditioning and remote renal preconditioning -: Identifying a protective factor using proteomic methods?
复制标题
DOI：
10.1007/s00395-005-0565-0
复制
发表时间：
2006-03-01
影响因子：
9.5
通讯作者：
Vogt, AM
中科院分区：
文献类型：
--
作者：
Lang, SC;Elsässer, A;Vogt, AM
远距离缺血预处理是通过体液机制还是神经机制从预处理到预处理组织的作用尚不清楚。以下研究的目的是确定一个可能的体液触发缺血心肌预适应和远程肾脏预适应。对开胸大鼠进行45分钟的冠状动脉闭塞期，然后再灌注2小时（对照动物; n = 6）。冠状动脉预处理组（IPC，n = 6）先行冠状动脉阻断5 min，再灌注5 min，重复3次。肾预处理组（IPR，n = 6）先阻断肾动脉10 min，再灌注20 min。在每个方案结束时测定危险区（AAR）和梗死区（IA）。在预处理方案结束时从平行实验中采集血样，使用二维凝胶电泳（2-DE）、基质辅助激光解吸和电离飞行时间质谱（MALDI-TOF-MS）和液相色谱-电喷雾电离-串联质谱（nanoLC-ESI-MS/MS）进行蛋白质组学分析。对照组中IA/AAR为87.8 ± 10.7%。IPC和IPR显著降低IA/AAR（58.2 +/- 9.3%和56.9 +/-9.0%，p < 0.001）。蛋白质组学分析检测到四个蛋白质点，其在预处理组与对照组相比上调（n = 3）或下调。艾德鉴定3个上调蛋白点为白蛋白片段，而下调蛋白点为肝再生相关蛋白（LRRG 03）。有趣的是，最近已经显示并评价了短暂缺血引起的白蛋白修饰用于亚致死性心肌缺血的临床诊断。然而，没有发现具有已知信号功能的差异丰富的蛋白质，因此，尽管IPC和IPR后血液中存在差异蛋白质表达，但我们的数据不支持分子量大于8 kDa的远程预适应体液介质。我们的研究结果，而不是建议一个神经源性通路或介质小于8 kDa。
It is still unknown whether remote ischemic preconditioning is mediated by a humoral or a neurogenic mechanism from the preconditioning to the preconditioned tissue. The purpose of the following study was to identify a possible humoral trigger of ischemic myocardial preconditioning and remote renal preconditioning. Open chest rats were subjected to a coronary artery occlusion period of 45 min followed by 2 h of reperfusion (Control animals; n = 6). The coronary preconditioned group (IPC, n = 6) was subjected to a preceding preconditioning period of 5 min coronary artery occlusion followed by 5 min of reperfusion, repeated three times. The renal preconditioned group (IPR, n = 6) was subjected to a preceding renal artery occlusion period of 10 min followed by 20 min of reperfusion. Area at risk (AAR) and infarcted area (IA) were determined at the end of each protocol. Blood samples were taken at the end of the preconditioning protocols from parallel experiments for proteomic analysis using two-dimensional gel electrophoresis (2-DE), matrix assisted laser desorption and ionization-time of flight-mass spectrometry (MALDI-TOF-MS), and liquid chromatography-electrospray ionization-tandem mass spectrometry (nanoLC-ESI-MS/MS). IA/AAR was 87.8 +/- 10.7% in the control group. IPC and IPR signi.cantly reduced IA/AAR (58.2 +/- 9.3% and 56.9 +/- 9.0%, p < 0.001). Proteomic analyses detected four protein spots which were either up- (n = 3) or down-regulated in the preconditioned groups vs. the control group. The three up-regulated protein spots were identi.ed as albumin fragments, whereas the downregulated spot was identified as liver regeneration-related protein (LRRG03). Interestingly, albumin modification by brief ischemia has been recently shown and evaluated for the clinical diagnosis of sublethal myocardial ischemia. However, no differentially abundant proteins which possess a known signaling function could be found. Hence, though there is a differential protein expression in blood following IPC and IPR, our data are not in favor of a humoral mediator of remote preconditioning with a molecular weight of more than 8 kDa. Our results rather suggest either a neurogenic pathway or a mediator smaller than 8 kDa.