POLY(ADP-RIBOSE) POLYMERASE INHIBITOR REDUCES HEART ISCHAEMIA/REPERFUSION INJURY VIA INFLAMMATION AND AKT SIGNALLING

Objectives 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 novel, potent PARP inhibitor, has been proved to have cardiac protective effects. However, the underlying mechanisms are still not thoroughly understood. In this study, we investigate the effect of DPQ on heart I/R injury and its potential mechanisms. Methods Studies were performed with I/R rats9 hearts. DPQ was used to inhibit the activate of PARP. The myocardial infarction size, cardiac function and cells apoptosis were detected. 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 during the I/R protocol. Results Our data showed that DPQ could reduce the rat heart I/R injury in vivo. Heart I/R caused a significant increase in PARP activity. Administration of DPQ could decrease the activation of PARP. At the same time, administration of DPQ could decrease myocardial infarction size from 60.97±4.22% to 39.03±3.94% (p Conclusions Our results suggested that the inhibition of PARP was able to reduce heart I/R injury. The protective effects of DPQ were associated with both inflammation and Akt signalling.