Cardioprotective Effects Of Intracerebroventricular Morphine Postconditioning Against Ischemia-Reperfusion Injury Of Rat Heart And Its Mechanism

Objective The cardioprotection of Ischemia Postconditioning and pharmacal postconditioning against the injury of Ischemia/Reperfusion is the most popular subject.This experiment want to investigate the effect of intracerebroventricular morphine postconditioning against ischemia-reperfusion injury in rat heart and the mechanism of the central nervous system opioid receptor via establish the intracerebroventricular catheter placement and myocardial ischemia/reperfusion models.Method This experiments divided into two parts.One part:Forty-two Sprague-Dawley Rats were established intracerebroventricular catheter placement and myocardial ischemia/reperfusion models and randomly assigned to 7 groups : Sham group(Sham),control group(CON), intravenous control group(IVCON),morphine postconditioning group (POC),intracereborventricular morphine postconditioning group(MOC).According to the dosage of intracerebroventricular morphine(3μg·kg-1,0.3μg·kg-1,0.03μg·kg-1), MOC group was assigned to three groups :MOC1, MOC2, MOC3. Sham group only receive the surgery.The rest group were subjected to 30minutes of ischemia fellowed by 120minutes reperfusion,In the control group,5 ul normal saline was infused for a period of 5 minutes just before reperfusion.POC group was used as a positive control and was elicited by three 10s coronary artery occlusion periods interspersed with 10s of reperfusion just before 2 hour reperfusion. Intraveous control group and intracerebroventricular morphine postconditioning involved 5 minute infusion of morphine via intraveous or intracerebroventricular. Infarct size(IS) ,a percentage of the area at risk (AAR) was determined by triphenyltetrazolium(TTC) staining. Cardiac TroponinI (cTnI) of serum was observed at 120min of reperfusion.The second part:To investigate the possible mechanism of intracerebroventricular morphine postconditioning against the ischemia/reperfusion.The groups also divided into 7 groups.as the same as the first part,After 120min reperfusion,we bring down the brain from the rat and decide the c-fos expression in nucleus of tractus solitarius by immunohistochemical method .Results Compared with CON, MOC(3,0.3,0.03μg·kg-1),POC decreased infart size and cTnI significantly(P<0.05,P<0.01).Intracerebroventricular morphine postcondition- -ing (MOC:3,0.3,0.03μg·kg-1) and POC markedly reduced IS/AAR from54.9±8.3% to 32.5±7.7%,37.2±6.4%,45.8±7.8% and 31.2±8.2% respectively.Also reduced cTnI from 73.2±9.5% to 39.3±6.6%,48.1±8.1%,61.8±8.7%,35.8±7.2%.There are no difference between IVCON(3μg·kg-1) and CON in IS/AAR and cTnI. Moreover, Compared with CON,POC and MOC(MOC1,MOC2,MOC3) reduced the number of c-fos positive cell in NTS significantly,which from 42±10 to16±5,12±5,15±6,24±7 (P<0.01,P<0.05).Conclusion intracerebroventricular morphine postconditioning against ischemia-reperfusion injury in rat heart and the cardioprotective effect may mediated via c-fos.