Cardioprotection of orientin against myocardial ischemia reperfusion injury through induction of autophagy / 中国药理学通报

ABSTRACT

Aim To investigate the role of autophagy in the cardioprotection by orientin and the relative molec-ular mechanisms in cell apoptosis and autophay. Meth-ods The isolated ischemia reperfusion ( I/R ) heart model was built firstly. The Experiments were divided into seven groups:control group, I/R group, different concentrations of orientin-treated group ( 1. 0 mg · kg-1 ,2. 0 mg· kg-1 ,4. 0 mg · kg-1 ) , autophagy in-hibitor group and resveratrol group. Hemodynamic in-dex were recorded by PowerLab, the activities of myo-cardial enzymes were detected through Biochemical an-alyzer, the ultrastructure changes and autophagosomes in myocardial cells were detected by electron microsco-py, the apoptosis was detected by TUNEL, and LC3 and Beclin1 protein levels of left ventricle were meas-ured by Western blot. Results Orientin at middle and high concentrations(2 and 4 mg·kg-1 ) induced auto-phagy shown by increased the number of autophago-somes, LC3-Ⅱ/LC3-Ⅰ ratio and Beclin 1 expression after ischemia-reperfusion. The induction of autophagy by orientin was correlated with enhanced cardiac func-tion and decreased apoptosis. But wortmannin, a kind of autophagy inhibitor, significantly attenuated the ori-entin-induced autophagy and increased apoptosis. Con-clusion The cardioprotection of orientin against myo-cardial ischemia reperfusion injury may be mediated through the inhibition of apoptosis and induction of au-tophagy.