[Poly (ADP-ribose) polymerase inhibition attenuates ischemia/reperfusion induced myocardial injury in rat via reducing myocardial nuclear factor κB activity].

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.

• Authors: Zhao-feng Song, Bo DU, Xiao-ping Ji
• Journal: Zhonghua xin xue guan bing za zhi (Zhonghua Xin Xue Guan Bing Za Zhi) Vol. 40 Issue 12 Pg. 997-1002 (Dec 2012) ISSN: 0253-3758 [Print] China
• PMID: 23363712 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Isoquinolines
• NF-kappa B
• Piperidines
• Poly(ADP-ribose) Polymerase Inhibitors
• Intercellular Adhesion Molecule-1
• 3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2H)-isoquinolinone
• Cyclooxygenase 2
• Ptgs2 protein, rat
• Poly(ADP-ribose) Polymerases
• Matrix Metalloproteinase 9
• Mmp9 protein, rat

Topics

• Animals
• Cyclooxygenase 2 (metabolism)
• Female
• Intercellular Adhesion Molecule-1 (metabolism)
• Isoquinolines (pharmacology)
• Matrix Metalloproteinase 9 (metabolism)
• Myocardial Reperfusion Injury (drug therapy, metabolism, pathology)
• Myocytes, Cardiac (metabolism)
• NF-kappa B (metabolism)
• Piperidines (pharmacology)
• Poly(ADP-ribose) Polymerase Inhibitors
• Poly(ADP-ribose) Polymerases (metabolism)
• Rats
• Rats, Wistar