The Effect Of PARP1 On The Expression Of Associated Inflammatory Cytokines In Rats' Myocardium After Myocardial Infarction

Objective To study the protein expression and activation of PARP1 in rats'myocardium after acute myocardial infarction , the protein expression of associated inflammatory cytokines in myocardium and the effect of PARP1 inhibitor 3-AB on improving ventricular remodeling in rats after acute myocardial infarction.Methods The MI models of rats were constructed and divided into three groups : (1) myocardial infarction group (MI) :only ligation of left anterior descending coronary artery (LAD) ; (2) 3-aminobenzene group (MI-3AB): ligation of left anterior descending coronary artery and Intra-peritoneal injection with 3-aminobenzamide (3-AB) 20 mg·kg - 1·d - 1 ; (3) Sham group ( sham) : no ligation of LAD .And the fourth group(N) are normal rats .Cardiac architecture and function were determined by the echocardiography. The protein expression of PARP1, IL-1β,IL-6,IL-10 and TNF-ɑin infarction and non-infarction regions was measured by immunohistochemical staining . PARP1 activation was determined by Universal Colorimetric PARP Assay Kit with Histone Coated Strip Wells .Results The echocardiography showed that the ejection fraction〔EF , (61.2±9.6)% versus (85.0±2.7) % and (46.5±10.4)% versus (85.7±2.4) %〕significantly decreased in MI group (P < 0.05) ,compared with sham group at 24 hour and 72 hour after acute myocardial infarction ,while the EF in 3-AB group markedly increased compared with MI group (P < 0.05)〔(87.8±2.6)% versus (61.2±9.6) % and (86.1±1.3% versus (46.5±10.4) %〕at 24 hour and 72 hour after AMI . The fractional shortening ,〔FS , (31.2±6.2 ) % versus (52.3±8.1 ) % and (24.8±6.2)% versus (50.0±3.1) %〕markedly decreased in MI group (P < 0.05) , compared with sham group at 24 hour and 72 hour after acute myocardial infarction , while the FS in 3-AB group markedly increased compared with MI group (P < 0.05)〔(53.4±3.0) % versus (31.2±6.2)% and (50.8±2.5) %versus (24.8±6.2)%〕at 24 hour and 72 hour after AMI . 3-AB obviously improved the ejection fraction and the fractional shortening ( P < 0.05) . The immunohistochemical staining revealed that , in the non-infarction and infraction regions, TNF-α,IL-1?, and IL-6 protein expression peaked at 72 hour to 1 week after infarction and decreased thereafter. While IL-10 bottomed out at 72 hour to 1 week after infarction and increased thereafter . The protein production of PARP1,IL-6 and TNF-ɑmarkedly increased in MI group compared with sham group at 72 hour and 1 week after acute myocardial infarction ( P < 0.05)。And compared with MI group, the protein expression of TNF-α,IL-1?, and IL-6 in 3-AB group has markedly decrease at 72 hour and 1 week after AMI( P < 0.05), and also IL-10 significantly decrease at 72 hour and 1 week ( P < 0.05)。After AMI, the protein activation of PARP1 increased rapidly and then decreased. The PARP1 activation markedly increased in MI group compared with sham group ( P < 0.05) at 24 hour, 72 hour and 1 week after acute myocardial infarction. The protein of PARP1 and inflammatory cytokines mainly located in live myocardial cells of non-infarction and infraction regions of rats after AMI , and 3-AB significantly decreased protein production of PARP1,IL-6 , TNF-ɑand IL-10 ( P < 0.05). There existed a positive correlation between increasing protein expression of PARP and proinflammatory cytokines IL-1β,IL-6 and TNF-ɑ(r=0.361(p=0.006),r=0.568(p=0.000),r=0.527(p=0.000)),while no correlation existed between PARP and anti-inflammatory cytokines IL-10. And 3-AB decreased significantly protein expression of PARP1,IL-6 and TNF-ɑand increased IL-10 markedly and improved cardiac function significantly.Conclusion PARP-1 has been involved in depressing cardiac function after acute myocardial infarction by regulating gene expression of inflammatory cytokines in non-infarction and infraction region. 3-AB improved ventricular remodeling in rats after AMI . The mechanism maybe related to the inhibition of the polymerase activation of PARP1 in regulating the expression of inflammatory cytokines after AMI.