Poly (ADP-ribose) polymerase inhibition attenuates ischemia/reperfusion induced myocardial injury in rat via reducing myocardial nuclear factor κB activity
10.3760/cma.j.issn.0253-3758.2012.12.004
- VernacularTitle:多二磷酸腺苷-核糖聚合酶在大鼠心肌缺血再灌注损伤中的作用及其对核转录因子κB活性和炎症因子表达的调节
- Author:
Zhao-Feng SONG
1
;
Bo DU
;
Xiao-Ping JI
Author Information
1. 271000,山东省泰安市中心医院心内科
- Keywords:
Myocardial reperfusion injury;
Poly(ADP-ribose) polymerases;
NF-kappa B;
Inflammation mediators
- From:
Chinese Journal of Cardiology
2012;40(12):997-1002
- CountryChina
- Language:Chinese
-
Abstract:
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.Method 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.Result (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).Conclusion 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.
