Minocycline postconditioning protects myocardium from ischemia-reper-fusion injury through attenuating poly(ADP-ribose) polymerase excessive activation / 中国病理生理杂志

ABSTRACT

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 morpho-logical 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 factorα( 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-αcontent and IL-1βconcentration 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-αcontent and IL-1βconcentration 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: Minocy-cline postconditioning may attenuate myocardial ischemia-reperfusion injury by depressing the activation of PARP-1 in car-diomyocytes and peripheral leukocytes in rats.