DCPIB attenuates myocardial ischemia/reperfusion injury through inhibiting autophagy in rat model

AIM To explore the possible mechanism of DCPIB (4-［(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy］ butanoic acid) in alleviating myocardial I/R injury. METHODS Sprague Dawley rats were randomly divided into sham operation group, I/R group, I/R+rapamycin (RAPA) group, I/R+DCPIB group, I/R+3-methyladenine (3MA, an autophagic inhibitor) group and I/R+RAPA+DCPIB group with six rats in each group. Ischemia was induced for 30 min followed by reperfusion for 24 h in rats. DCPIB (10 mg/kg), RAPA (4 mg/kg) and 3MA (1 mg/kg) were administered with intraperitoneal injection 10 min before the onset of reperfusion, respectively. Serum myocardial enzymes were measured and light microscopic study was performed. Myocardial LC3 was detected by immunohistochemistry. Nuclear factor-κB (NF-κB) and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS Expressions of myocardial LC3, TNFα and NF-κB significantly increased (P<0.05) and cardiac functions declined in I/R group compared with those in sham operation group (P<0.05). Myocardial LC3 further increased in RAPA group, which was reversed using 3MA, an autophagic inhibitor. Of note, DCPIB administration caused a significant reduction of myocardial LC3, TNF-α and NF-κB (P<0.05), significantly improved cardiac functional recovery and reduced myocardial enzyme activity compared with those in I/R group and I/R+RAPA+DCPIB group (P<0.05). Compared with those in sham-operated group, left ventricular systolic pressure (LVSP), maximal rate of ventricular pressure (+dp/dtmax) increased and maximal rate of ventricular pressure decreased (-dp/dtmax), whereas left ventricular end diastolic pressure (LVEDP) significantly increased in I/R group and I/R+RAPA group (P<0.05). DCPIB reversed the disorder. CONCLUSION Our results demonstrate that DCPIB attenuates myocardial ischemia/reperfusion injury through inhibiting autophagy.