Effects of heme oxygenase-1 mediated by cell penetrating peptide PEP-1 on myocardial ischemia/reperfusion injury in isolated rat hearts

Abstract

Objective To investigate the protective effects of heme oxygenase-1 （HO-1） mediated by cell penetrating peptide PEP-1 on myocardium against ischemia/reperfusion （IR） injury in isolated rat hearts. Methods Healthy male SD rats weighing 220-280 g were anesthetized with intraperitoneal pentobarbital. Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95%O2-5% CO2 at 37 ℃. Eighteen isolated rat hearts were randomly divided into 3 groups （ n = 6 each）： Ⅰ group sham operation （group S）;Ⅱ group IR and Ⅲ group PEP-1/HO-1 ＋ IR （group HO-1）. The isolated rat hearts were perfused with an oxygena-ted （95% O2-5% CO2 ） K-H solution at 37 ℃ in a Langendorff apparatus and were subjected to 40 min of global ischemia followed by 50 min of reperfusion after 30 min of stabilization. In group Ⅲ （group HO- 1 ） the isolated hearts were perfused with 50 μmol/L PEP-1/HO-1 for 15 min before ischemia. After 50 min of reperfusion, HO-1expression, MDA content and SOD activity in myocardial tissues were determined. The activities of creatine kinase （CK） and lactic dehydrogenase （LDH） in coronary effluent fluid were measured. Results The HO- 1 expression was significanfly higher in HO-1 group than in group IR. IR induced significant increase in MDA content and decrease in SOD activity in myocardium and CK and LDH activities in coronary effluent in group Ⅱ compared with group S. PEP-1/HO-1 significantly attenuated IR-induced changes. Conciusion HO-1 mediated by PEP-1 has protective effects on myocardium ngainst IR injury in rats. Key words: Heme oxygenase（decyclizing）; Cell penetrating peptides; Myocardial reperfusion injury