Minocycline postconditioning protects myocardium from ischemia-reperfusion injury through attenuating poly(ADP-ribose) polymerase excessive activation

AIM: To investigate whether minocycline postconditioning protects rat myocardium from ischemia-reperfusion (I/R) injury through attenuating poly(ADP-ribose)polymerase-1(PARP-1) excessive activation. METHODS: The left anterior descending coronary artery was ligated for 45 min and then reopened for 2 h to establish the rat model of myocardial ischemia-reperfusion injury. The male Wistar rats (n=90) were randomly divided into sham group, I/R group, low-and high-dose minocycline groups, and 3-aminobenzamide (3-AB, PARP inhibitor) group. The myocardial infarct size was measured by Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining. The morphological changes of the myocardium were observed with HE staining. The cardiomyocyte apoptosis was detected using in situ TDT-mediated dUTP nick end labeling (TUNEL). The level of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in the serum were measured by ELISA. The content of poly(ADP-ribose) (PAR) in the reperfused myocardium and peripheral leukocytes were detected by Western blot. RESULTS: Compared with sham group, PAR expression, TNF-α content and IL-1β concentration increased in all other groups. Compared with I/R group, treatment with low and high doses of minocycline and 3-AB significantly reduced the infarct size and myocardial apoptosis. PAR expression, TNF-α content and IL-1β concentration in low-and high-dose minocycline groups and 3-AB group all decreased. No significant difference of the above parameters between high-dose minocycline group and 3-AB group was observed. CONCLUSION: Minocycline postconditioning may attenuate myocardial ischemia-reperfusion injury by depressing the activation of PARP-1 in cardiomyocytes and peripheral leukocytes in rats.