title: Poly (ADP-ribose) polymerase inhibitor reduces heart ischaemia/reperfusion injury via inflammation and Akt signalling in rats.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Taian Central Hospital, Taian, Shandong 271000, China. szhf73@126.com
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Song
authors.forename: Dong-Yu
authors.initials: DY
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: DU
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Ji
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D007546:Isoquinolines / Q000627:therapeutic use*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D010880:Piperidines / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010880:Piperidines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C108729:3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone; D051057:Proto-Oncogene Proteins c-akt