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[Poly (ADP-ribose) polymerase inhibition attenuates ischemia/reperfusion induced myocardial injury in rat via reducing myocardial nuclear factor κB activity].
- Source :
-
Zhonghua xin xue guan bing za zhi [Zhonghua Xin Xue Guan Bing Za Zhi] 2012 Dec; Vol. 40 (12), pp. 997-1002. - Publication Year :
- 2012
-
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.<br />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.<br />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).<br />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.
- Subjects :
- Animals
Cyclooxygenase 2 metabolism
Female
Intercellular Adhesion Molecule-1 metabolism
Isoquinolines pharmacology
Matrix Metalloproteinase 9 metabolism
Myocardial Reperfusion Injury drug therapy
Myocardial Reperfusion Injury pathology
Myocytes, Cardiac metabolism
Piperidines pharmacology
Poly(ADP-ribose) Polymerase Inhibitors
Rats
Rats, Wistar
Myocardial Reperfusion Injury metabolism
NF-kappa B metabolism
Poly(ADP-ribose) Polymerases metabolism
Subjects
Details
- Language :
- Chinese
- ISSN :
- 0253-3758
- Volume :
- 40
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Zhonghua xin xue guan bing za zhi
- Publication Type :
- Academic Journal
- Accession number :
- 23363712