Minocycline has been shown to protect against myocardial ischemia and reperfusion injury. However, the mechanism remains unclear. This study was to investigate the role of high mobility group box 1 protein (HMGB1) in the cardioprotection of minocycline during myocardial ischemia and reperfusion in rats. Anesthetized male rats were once treated with minocycline (45 mg/kg, i.p.) 1h before ischemia, and then subjected to ischemia for 30 min followed by reperfusion for 4h. The lactate dehydrogenase (LDH), creatine kinase (CK) and infarct size were measured and the myocardial tissue apoptosis was assessed by TUNNEL assay. Neonatal rat ventricular myocytes were prepared and then cultured with recombinant HMGB1. Cell apoptosis was measured using an annexin V-FITC apoptosis detection kit. HMGB1 expression was assessed by immunoblotting. After 4h of reperfusion, minocycline could significantly decrease the infarct size, myocardium apoptosis and the levels of LDH and CK (all P<0.05). Meanwhile, minocycline could also significantly inhibit the HMGB1 expression during myocardial ischemia and reperfusion compared to that in ischemia and reperfusion group (P<0.05). In vitro, HMGB1 could significantly decrease the cell viability and promote the apoptosis of neonatal myocytes in a dose-dependent manner. The present study suggested that minocycline could protect against myocardial ischemia and reperfusion injury by inhibiting HMGB1 expression.
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