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兔冠状动脉侧支循环形成过程中间歇性心肌缺血后左心室组织的蛋白质组学分析

Proteomic analysis of left ventricular tissues following intermittent myocardial ischemia during coronary collateralization in rabbits.

作者信息

Gu Jinyang, Wang Yuanhui, Li Jianan, Wang Jun, Jin Tingjian

机构信息

Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Int J Cardiol. 2009 Jan 24;131(3):326-35. doi: 10.1016/j.ijcard.2007.10.054. Epub 2008 Jan 22.

Abstract

BACKGROUND

Repeated transient myocardial ischemia may offer favorable effects to coronary perfusion via collateral circulation, although the underlying molecular mechanisms still remain unclear. This study was designed to evaluate the proteomic changes during this process.

METHODS

Rabbits were randomly divided into sham-operated and ischemic groups (5 each) and were subjected to intermittent myocardial ischemia by inflation or deflation of pneumatic occluders for 4 weeks to establish a controlled myocardial ischemic model. Isolated hearts were subjected to histological observation, microspheric detection, capillary counting and proteomic analysis.

RESULTS

Elevation of ST segment or back to normal in Lead-II electrocardiogram could be induced by occluders without overt histological and cardiac troponin I alterations. Regional coronary collateral blood flow exhibited a remarkable increase following intermittent inflation of occluders in the ischemic group (P<0.01). Simultaneously, capillary numbers per unit area were significantly different between groups (P<0.01). Twenty-three differentially expressed protein spots were separated by two-dimensional gel electrophoresis and 13 out of them were identified by MALDI-TOF-MS.

CONCLUSION

The present study indicates that the differentially expressed proteins involved in proliferation, growth and energy metabolism following intermittent myocardial ischemia without ischemia-reperfusion injury are likely associated with the development of collateralization beneficial to coronary circulation.

摘要

背景

反复短暂性心肌缺血可能通过侧支循环对冠状动脉灌注产生有利影响,尽管其潜在分子机制仍不清楚。本研究旨在评估这一过程中的蛋白质组学变化。

方法

将兔子随机分为假手术组和缺血组(每组5只),通过气动闭塞器充气或放气对其进行间歇性心肌缺血4周,以建立可控的心肌缺血模型。对离体心脏进行组织学观察、微球检测、毛细血管计数和蛋白质组学分析。

结果

闭塞器可诱导II导联心电图ST段抬高或恢复正常,且无明显组织学和心肌肌钙蛋白I改变。缺血组在闭塞器间歇性充气后,局部冠状动脉侧支血流显著增加(P<0.01)。同时,两组单位面积的毛细血管数量有显著差异(P<0.01)。通过二维凝胶电泳分离出23个差异表达的蛋白点,其中13个通过基质辅助激光解吸电离飞行时间质谱鉴定。

结论

本研究表明,间歇性心肌缺血后,在无缺血再灌注损伤情况下,参与增殖、生长和能量代谢的差异表达蛋白可能与有利于冠状动脉循环的侧支循环形成有关。

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