Activated protein C protects myocardium via activation of anti-apoptotic pathways of survival in ischemia-reperfused rat heart.
Activated protein C protects myocardium via activation of anti-apoptotic pathways of survival in ischemia-reperfused rat heart.
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DOI：
10.3346/jkms.2010.25.11.1609
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发表时间：
2010-11
影响因子：
4.5
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Ding JW;Tong XH;Yang J;Liu ZQ;Zhang Y;Yang J;Li S;Li L
活化蛋白C（APC）对心肌缺血再灌注损伤有保护作用。然而，APC的保护机制并不完全清楚。本研究旨在探讨APC对心肌缺血损伤的影响及其可能机制。对经呼吸机通气的麻醉的Sprague-Dawley大鼠进行30分钟的左前降支冠状动脉闭塞，随后进行2小时的再灌注。将大鼠随机分为Sham组、I/R组、APC预处理组和后处理组。检测心肌梗死面积、细胞凋亡指数、ERK 1/2、Bcl-2、Bax和细胞色素c基因和蛋白磷酸化水平。在APC给药的大鼠心脏，无论给药的时间，梗死面积始终减少缺血/再灌注（I/R）大鼠相比。APC可提高I/R大鼠ERK 1/2和抗凋亡蛋白Bcl-2的表达，而这些蛋白在I/R大鼠中明显减少。APC降低促凋亡基因Bax和细胞色素c的表达。这些发现表明，APC通过保留参与抗凋亡途径的蛋白质和基因的表达而产生心脏保护作用，而与给药的时间无关。
Activated protein C (APC) is known to be beneficial on ischemia reperfusion injury in myocardium. However, the protection mechanism of APC is not fully understood. The purpose of this study was to investigate the effects and possible mechanisms of APC on myocardial ischemic damage. Artificially ventilated anaesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 hr of reperfusion. Rats were randomly divided into four groups; Sham, I/R, APC preconditioning and postconditioning group. Myocardial infarct size, apoptosis index, the phosphorylation of ERK1/2, Bcl-2, Bax and cytochrome c genes and proteins were assessed. In APC-administrated rat hearts, regardless of the timing of administration, infarct size was consistently reduced compared to ischemia/reperfusion (I/R) rats. APC improved the expression of ERK1/2 and anti-apoptotic protein Bcl-2 which were significantly reduced in the I/R rats. APC reduced the expression of pro-apoptotic genes, Bax and cytochrome c. These findings suggest that APC produces cardioprotective effect by preserving the expression of proteins and genes involved in anti-apoptotic pathways, regardless of the timing of administration.
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