Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
Shock. 2012 May;37(5):492-500. doi: 10.1097/SHK.0b013e31824989d7.
The overactivation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is considered a final common effector in ischemia/reperfusion (I/R) injury. The aim of the current study was to examine the precise time course of the activation of PARP in peripheral leukocytes and the reperfused myocardium tissue on myocardial I/R injury from the same rat and to identify the relationship between myocardial infarct size and the degree of PARP activation in circulating leukocytes. Another aim of the study was to test the effect of 3-aminobenzamide (a well-known and widely used PARP inhibitor) on the activation of PARP in the reperfused myocardium and peripheral leukocytes. Poly(ADP-ribose) polymerase activation was measured by Western blotting for its product, poly(ADP-ribose) (PAR). The localization of PARP activation was determined by PAR immunohistochemistry. The results showed that poly(ADP-ribosyl)ation was detected 15 min, peaked 2 to 6 h, and remained markedly detectable 24 h in the reperfused heart after I/R model. Similarly, PAR content of the leukocytes increased in cells isolated just after reperfusion from the same rat. Immunohistochemical studies localized the staining of PAR primarily to the cardiac myocytes and vascular endothelial cells. At 6 h, there was a significant linear correlation between infarct size and PARP activity, whereas at 2 and 24 h, no relationship was found. The PARP inhibitor 3-aminobenzamide (3-AB, 20 mg kg⁻¹ i.v. injection 15 min before reperfusion, and every 2 h thereafter for 6 h) markedly reduced infarct size through depressing the activation of the enzyme in myocytes and peripheral leukocytes even when the treatment is initiated at 2 h after reperfusion.
聚（ADP-核糖）聚合酶（PARP）的过度激活被认为是缺血/再灌注（I/R）损伤的最终共同效应器。本研究的目的是从同一大鼠中检测外周白细胞和再灌注心肌组织中 PARP 激活的确切时间过程，并确定循环白细胞中 PARP 激活程度与心肌梗死面积之间的关系。研究的另一个目的是测试 3-氨基苯甲酰胺（一种众所周知且广泛使用的 PARP 抑制剂）对再灌注心肌和外周白细胞中 PARP 激活的影响。通过 Western blot 检测其产物聚（ADP-核糖）（PAR）来测量 PARP 的激活。通过 PAR 免疫组化确定 PARP 激活的定位。结果表明，在 I/R 模型后再灌注的心脏中，聚（ADP-核糖基）化在 15 分钟时检测到，在 2 至 6 小时达到峰值，并且在 24 小时内仍明显可检测到。同样，从同一大鼠中分离的再灌注后即刻的白细胞中 PAR 含量增加。免疫组织化学研究将 PAR 的染色主要定位在心肌细胞和血管内皮细胞上。在 6 小时时，梗死面积与 PARP 活性之间存在显著的线性相关性，而在 2 小时和 24 小时时，未发现相关性。PARP 抑制剂 3-氨基苯甲酰胺（3-AB，再灌注前 15 分钟静脉注射 20mg/kg，此后每 2 小时注射一次，共 6 小时）通过抑制心肌细胞和外周白细胞中酶的激活，显著降低梗死面积，即使在再灌注后 2 小时开始治疗也是如此。
