[Poly (ADP-ribose) polymerase inhibition attenuates ischemia/reperfusion induced myocardial injury in rat via reducing myocardial nuclear factor κB activity].
OBJECTIVE
To investigate the effect of Poly (ADP-ribose) polymerase (PARP) inhibition on ischemia/reperfusion (I/R) induced myocardial injury in rat and related mechanisms.


METHODS
Adult Wistar rats were randomly divided into sham-control (n = 18), I/R (60 min ischemia followed by 180 min reperfusion, n = 18) and I/R + PARP inhibitor 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), 10 mg/kg, i.p. injection at 1 h before I/R (n = 18). Myocardial expression of PARP, infarct size, and cardiomyocytes apoptosis were determined. Additionally, myocardial NF-κB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9 at protein and mRNA level were detected.


RESULTS
(1) Myocardial expression of PARP was significantly upregulated in I/R group compared to sham-control group, which could be significantly reduced by pretreatment with DPQ (P < 0.05 vs. I/R group). (2) Infarct size [(31.45 ± 5.54)% vs. (45.97 ± 4.22)%] and cardiomyocytes apoptosis [(23.0 ± 3.8)% vs. (34.0 ± 6.2)%] were significantly reduced by pretreatment with DPQ (all P < 0.05 vs. I/R group). (3) Pretreatment with DPQ also significantly decreased the NF-κB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9 at both protein and mRNA level (all P < 0.05).


CONCLUSIONS
The expression of PARP, NF-κB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9 are upregulated in I/R induced myocardial injury. PARP inhibitor DPQ could attenuate I/R induced myocardial injury through reducing NF-κB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9.
Department of Cardiology, Tai'an Central Hospital, Tai'an 271000, China. szhf73@126.com
Zhao-feng
ZF
Song
Bo
B
DU
Xiao-ping
XP
Ji
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007546:Isoquinolines; D016328:NF-kappa B; D010880:Piperidines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D018799:Intercellular Adhesion Molecule-1; C108729:3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D011065:Poly(ADP-ribose) Polymerases; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat