| The preventions for acute ischemia -reperfusion injury have been hot spots of revascularization therapies research of acute myocardial infarction for a long time. Mechanical ischemic Post-conditioning, a series of brief mechanical coronary interruptions and reperfusion sequences applied at the very onset of reperfusion , has become a promising protective strategy to the heart of acute ischemia-reperfusion. Post-conditioning is more likely than preconditioning to be feasible as a clinical application to patients undergoing percutaneous coronary intervention for acute myocardial infarction because of it can be predictable and controlled easily.Pharmacological post-conditioning means applying mimetic protective agents at the very onset of reperfusion after ischemia procedure to protect the heart from reperfusion injury. Reperfusion after a period of ischemia is associated with the formation of reactive oxygen species (ROS) leading to myocardium cell damage. Although endogenous antioxidants are activated because of oxidative stress following ischemia, their levels are not high enough to prevent reperfusion injury. Hence there is a essential need for exogenous supplement of antioxidants to the heart of acute ischemia-reperfusion. Here is the concise introduction of the research.Objective Regarding post-conditioning as positive control, to evaluate the influence on the myocardial ischemia/reperfusion injury of pharmacological post-conditioning with a new free radical scavenger-Edaravone, in rat model and investigate corresponding mechanisms of regulator proteinases for mycardial cell apoptosis. Methods Experimental model was established in anesthetized open-chest rats by ligating coronary artery with PTCA balloon, the left anterior descending artery was occluded for 45 min and reperfused for 3 hours. Male Wistar rats were randomly divided into five groups: (1) sham operation;(2)standard ischemia/reperfusion; (3)Myocardial mechanical ischemic post-conditioning ; (4) Edaravone 10mg/kg , injected intra aortic sinus 1 min before reperfusion (iA);(5) Edaravone 10 mg/kg , injected intra femoral vein 1 min before reperfusion (iV). ECG changes and dynamic parameters were monitored during the procedure, plasma CK-MB,biochemical markers—MDA,SOD,NO in plasma as well as in myocardial tissue homogenate of every groups were assessed and evaluated at the end of reperfusion. Ischemic size and infarct size were measured by Evans blue staining and TTC staining, respectively. And the expression of bax,bcl-2 and caspase-8 were assayed by Western blotting. Results Myocardial infarct size and levels of CK-MB in plasma were significantly reduced and MDA activities in plasma and tissue homogenate were significantly decreased in group I-postC and group-iA, compared with group I/R (p<0.01), activity of NO was decreased and SOD was enhanced(p<0.05). MI size and level of CK-MB,MDA were reduced, activity of SOD was enhanced in group-iV, compared with I/R group(p<0.05). There are no statistical differences in the MI size and biochemical parameters above-mentioned in I-postC,Edaravone iA and iV group (p > 0.05). The expressions of bax and caspase-8 were decreased , the expression of bcl-2 was enhanced in group I-postC and group Edaravone, compared with group I/R (p<0.05). Conclusion Mechanical post-conditioning and Edaravone pharmacological post-conditioing applied just before the onset of coronary reperfusion provides potent reduction of myocardial infarct size. Intra aorta root-coronary passway injection showed similar effect with intra vein, it might be a suitable pharmacological post-conditioing pathway in clinic. The common potential protective mechanism of mechanical post-conditioning and Edaravone pharmacological post-conditioing might be associated with the decreasing of myocardium injury by reactive oxygen species and strengthening the resistance to oxidation stress. The molecule mechanism might related to regulation of the activities of the proteinases of cell apoptosis, I.e. depressing caspase cascade pathway and down-regulating the apoptotic index (Bax/ Bcl-2)... |
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