Exendin-4 attenuates myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein expression.

BACKGROUND

High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia and reperfusion (I/R) injury. Exendin-4 (Ex-4), glucagon-like peptide-1 receptor agonist, has been reported to attenuate myocardial I/R injury. This study was to investigate the potential mechanism by which Ex-4 attenuates myocardial I/R injury in rats.

METHODS

Anesthetized male rats were once treated with Ex-4 (5 μg/kg, i.v.) 1 h before ischemiain the absence and/or presence of exendin (9-39) (an antagonist for glucagon-like peptide-1 receptor, 5 μg/kg, i.v.), and then subjected to ischemia for 30 min followed by reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) activity and infarct size were measured. HMGB1 expression was assessed by immunoblotting.

RESULTS

The results showed that pretreatment of Ex-4 could significantly decrease the infarct size and the levels of LDH and CK after 4 h reperfusion (all p < 0.05). Ex-4 could also significantly inhibit the increase of the MDA level, the decrease of the SOD level (both p < 0.05). Meanwhile, Ex-4 could significantly inhibit HMGB1 expression induced by I/R. Administration of exendin (9-39) could abolish the protective effect of Ex-4 (all p < 0.05).

CONCLUSIONS

The present study suggested that Ex-4 could attenuate myocardial I/R injury which may be associated with inhibiting HMGB1 expression.