Protection Of Nuclear Factor-κB Inhibitor-PDTC To Immature Myocardial Ischemia-reperfusion Injury Of Neonatal Rabbits

Objective: by establishing the neonatal rabbits myocardial ischemia-reperfusion injury model ex vivo,the effect of NF-κB inhibitor PDTC used to the myocardial ischemical-reperfusion injury of neonatal rabbits is studied. The expression of NF-κB in the myocard of ischemical reperfusion injur of neonatal rabbits is detected,the possible effect of actived NF-κB in the myocard of ischemia-reperfusion injury of neonatal rabbits is approached.Methods:This study established the neonatal rabbits myocardial ischemia-reperfusion injury model using Langendorf isolated heart perfusion system.Thirty-two pure breed New Zealand neonatal rabits of 3-4 weeks were divided into four groups, control group A which were only used cool crystalline body of St thomas cardioplegic solution to perfuse during the ischemia , experiment B, which were added to some dosage of PDTC , behind ischemia . during the ischemia cool crystalline body of St thomas cardioplegic solution is used, group B were divided into three groups according to the different dosage of PDTC: B1,B2,B3.This study was aimed to detect the heart functional parameter by ALC-MPA multichannel biology signal analysis system when in the 15min,30min.60min after heart rejumping : HR, LVPSP,left ventricular pressure upgrade max(+dp/dtmax), corona flow postischemia 15 min , CK-MB ,LDH;the concentration of MDA,SOD and ATP on the left ventricle constitution; the changes of myocardial ultramicrostructure by light microscope and electron microscope;calculating myocardial cell apoptotic index by TUNEL. The expression of NF-κB in the myocard of ischemical reperfusion injur of neonatal rabbits is detected by immunohistochemistry.Results: 1. Before the ischemic,experiment and control groups had no significant differences (P>0.05) on the heat functional parameter(HR,LVPSP,+dp/dtmax,CF);Reperfusion, the heart function recovery ofexperiment group of 15min,30min,60min were better than control group,especially in B2,B3. 2. Before the ischemic,experiment and control groups had no significant differences (P>0.05) on the CK-MB,LDH. The values of CK-MB,LDH dropped obviously (P<0.05),especially in B3(P<0.05).3. It had statistic differences of the values of ATP, MDA and SOD while comparing experiment groups and control groups (P<0.05). the values of ATP,SOD increased more distinctly (p<0.05)while droped in control groups(p<0.05),especially in B3.4. Myocardial ishemia-reperfusion placed a premium on the apoptosis of cardiac muscle cell. No signs of apoptosis of cardiac muscle cell in group B1 and control group were found and no statistic differences of AI (P>0.05) were presented. While the apoptosis of cardiac muscle cell were obviously found in group B2, B3 and statistic differences of AI (P<0.05) were presented, group B3 was the minimum and had significant statistic differences of AI (P<0.01).5. The expression level of NF-κB in control group is high,and is decreased in experiment group, The expression level of NF-κB in group B3 is lowest. 6. under the light microscope and electron microscope,the injury of control group myocardial pathology changed obviously ,the injury of ultramicrostructure was lightened compared with experiment group and control group ,especially group B3. Conclutions: (1) PDTC could improve the ventricular fibrillation,descrease cardiac enzymes leakage and induce Oxygen Free Radical (OFR) ,improve the ability of cardiac muscle cell energy metabolism , relieve the injure of the cardiac muscle ultramicrostructure , suppress the apposistance of myocardialcellafter the myocardial ischemical reperfusion injur.(2) PDTC has the protection effective to the Neonatal Rabbits after myocardial ischemia-reperfusion injury which might be assossiated with the activetion of NF-κB.