Department of Cardiology, Taian Central Hospital, Taian, Shandong 271000, China.
Chin Med J (Engl). 2013;126(10):1913-7.
Poly (ADP-ribose) polymerase (PARP) has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), a potent PARP inhibitor, has cardiac protective effects. Because the underlying mechanisms are not understood, we investigated the effect of DPQ on heart I/R injury and its mechanisms.
Studies were performed with I/R rats' hearts. DPQ was used to inhibit the activation of PARP. Cardiac function and cellular apoptosis were assessed. The activation of PARP, transcription factor nuclear factor-kappaB (NF-κB), intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) were evaluated. We also evaluated expression of Akt and two of its downstream targets, glycogen synthase kinase-3β (GSK-3β) and forkhead transcription factor FOXO3a.
Administration of DPQ significantly decreased the activation of PARP and cellular apoptosis from (35 ± 5)% to (20 ± 4)% and simultaneously improved the cardiac function. DPQ reduced the expressions of NF-κB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a.
The protective effects of DPQ were associated with the suppression of inflammation and the activation of the Akt signalling pathways suggesting that the inhibition of poly (ADP-ribose) polymerase reduced heart I/R injury in rats.
聚（ADP-核糖）聚合酶（PARP）被认为在心肌缺血/再灌注（I/R）损伤的发病机制中发挥重要作用。3,4-二氢-5-[4-（1-哌啶基）丁氧基]-1（2H）-异喹啉酮（DPQ），一种有效的 PARP 抑制剂，具有心脏保护作用。由于其潜在机制尚不清楚，我们研究了 DPQ 对心肌 I/R 损伤及其机制的影响。
用 I/R 大鼠心脏进行研究。DPQ 用于抑制 PARP 的激活。评估心脏功能和细胞凋亡。评估 PARP、转录因子核因子-κB（NF-κB）、细胞间黏附分子-1（ICAM-1）、环氧化酶-2（COX-2）和基质金属蛋白酶-9（MMP-9）的激活。我们还评估了 Akt 及其两个下游靶点糖原合酶激酶-3β（GSK-3β）和叉头转录因子 FOXO3a 的表达。
DPQ 的给药显著降低了 PARP 的激活和细胞凋亡，从（35±5）%降至（20±4）%，同时改善了心脏功能。DPQ 降低了大鼠心脏中 NF-κB、ICAM-1、COX-2 和 MMP-9 的表达，并促进了磷酸化-Akt、磷酸化-GSK-3β 和磷酸化-FOXO3a 的激活。
DPQ 的保护作用与抑制炎症和激活 Akt 信号通路有关，表明抑制聚（ADP-核糖）聚合酶可减轻大鼠心肌 I/R 损伤。
