OBJECTIVE: To investigate the role of mitochondrial permeability transition pore (MPTP) opening in mediating the effect of endomorphine-1 postconditioning to alleviate myocardial ischemia-reperfusion (IR) injury in rats. METHODS: Forty-five male SD rats were randomized equally for sham operation, myocardial IR injury, endomorphin-1 postconditioning, atractyloside (a MPTP opener) postconditioning, or endomorphin-1 + atractyloside postconditioning. The hemodynamic param-eters of the rats were monitored in real time via carotid artery cannulation to the left ventricle. After reperfusion, plasma samples were collected for biochemical analyses. The size of myocardial infarct area was detected using Evans blue and TTC double staining, and the myocardial expressions of apoptosis-related proteins Bax, Bcl-2 and cleaved caspase-3 were analyzed using Western blotting. RESULTS: Myocardial IR injury resulted in significantly decreased heart rate and blood pressure in the rats (P<0.05). Compared with those in IR group, the rats with endomorphin-1 postconditioning showed significantly increased heart rate and blood pressure (P<0.05), lowered contents or activities of LDH, CK-MB, cTnI, IL-6, TNF-α, Cyt-C and MDA in the plasma (P<0.05), increased plasma SOD activity (P<0.05), reduced size of myocardial infarction, decreased myocardial expression of Bax and cleaved caspase-3 protein (P<0.05), and increased myocardial expression of Bcl-2 protein (P<0.05). All these changes induced by endomorphin-1 were obviously reversed by atractyloside postconditioning (P<0.05). CONCLUSION: Endomorphin-1 postconditioning protects against myocardial IR injury in rats probably by inhibiting the opening of MPTP and reducing cardiac myocyte apoptosis via down-regulating cleaved caspase-3 expression.
OBJECTIVE: To investigate the role of mitochondrial permeability transition pore (MPTP) opening in mediating the effect of endomorphine-1 postconditioning to alleviate myocardial ischemia-reperfusion (IR) injury in rats. METHODS: Forty-five male SD rats were randomized equally for sham operation, myocardial IR injury, endomorphin-1 postconditioning, atractyloside (a MPTP opener) postconditioning, or endomorphin-1 + atractyloside postconditioning. The hemodynamic param-eters of the rats were monitored in real time via carotid artery cannulation to the left ventricle. After reperfusion, plasma samples were collected for biochemical analyses. The size of myocardial infarct area was detected using Evans blue and TTC double staining, and the myocardial expressions of apoptosis-related proteins Bax, Bcl-2 and cleaved caspase-3 were analyzed using Western blotting. RESULTS: Myocardial IR injury resulted in significantly decreased heart rate and blood pressure in the rats (P<0.05). Compared with those in IR group, the rats with endomorphin-1 postconditioning showed significantly increased heart rate and blood pressure (P<0.05), lowered contents or activities of LDH, CK-MB, cTnI, IL-6, TNF-α, Cyt-C and MDA in the plasma (P<0.05), increased plasma SOD activity (P<0.05), reduced size of myocardial infarction, decreased myocardial expression of Bax and cleaved caspase-3 protein (P<0.05), and increased myocardial expression of Bcl-2 protein (P<0.05). All these changes induced by endomorphin-1 were obviously reversed by atractyloside postconditioning (P<0.05). CONCLUSION: Endomorphin-1 postconditioning protects against myocardial IR injury in rats probably by inhibiting the opening of MPTP and reducing cardiac myocyte apoptosis via down-regulating cleaved caspase-3 expression.
Authors: G Petrosillo; N Di Venosa; N Moro; G Colantuono; V Paradies; E Tiravanti; A Federici; F M Ruggiero; G Paradies Journal: Free Radic Biol Med Date: 2010-12-03 Impact factor: 7.376