Butorphanol attenuates myocardial ischemia reperfusion injury through inhibiting mitochondria-mediated apoptosis in mice.

OBJECTIVE: To investigate the role of the opioid receptors agonist butorphanol on mice myocardial ischemia reperfusion (I/R) injury. MATERIALS AND METHODS: The left anterior descending of coronary artery was ligatured for 30 min and then reperfusion for 6 h was performed to mimic the mouse myocardial I/R injury. All mice were randomly divided into three groups: sham group, I/R group and I/R+ butorphanol group. Blood samples were collected for the measurement of cardiac troponin I (CTnI) and creatine kinase MB (CK-MB) levels. The infarct size was stained by triphenyltetrazolium chloride. The mitochondria morphology was observed by electron microscopy. The expressions of cleaved caspase-9 and -3, p38, ERK and JNK were detected by Western blot. RESULTS: The myocardial infarct size, serum CK-MB and CTn I levels, expression of cleaved caspase-9 and -3, phosphorylation of p38 and JNK were all increased in the I/R group compared with the sham group (all p < 0.01). Butorphanol reduced the myocardial infarct size, serum CTn I and CK-MB levels, expression of cleaved caspase-9 and -3, and phosphorylation levels of p38 and JNK (all p < 0.01). The number of mitochondria and the individual mitochondrial cross-sectional areas were decreased in the I/R mice compared with the sham-operated mice (all p < 0.01). Butorphanol reversed these changes in mitochondriay morphology (all p < 0.01). CONCLUSIONS: Butorphanol attenuates myocardial I/R injury through reducing cardiomyocyte apoptosis by inhibiting mitochondria-mediated apoptotic pathway, and blockage of p38 and JNK phosphorylation.