Abstract:

Objective To investigate the effect of heme oxygenase-1 (HO-1) on protection of myocardial cells by resveratrol (RES) against doxorubicin (DOX)-induced apoptosis. Methods Sixty male C57BL/6J mice were randomly divided into control group, DOX group, DOX+RES group and DOX+RES+HO-1 inhibitor ZnPP group, with 15 mice in each group. Except for control group, model of myocardial damage was established in the other groups by intraperitoneal  injection of DOX (total dosage, 12 mg/kg). Histopathological changes of myocardial tissues were observed by light microscopy with HE staining. The activity of serum creatine kinase (CK) and lactate dehydrogenase (LDH) was determined by chemiluminescent method, the activity of HO-1 and Caspase 3 in myocardial tissues was detected by spectrophotometry, the expression of HO-1 protein in myocardial tissues was determined by Western blotting, the expression of apoptosis-related proteins Bcl-2 and Bax in myocardial tissues was detected by immunohistochemistry, and the apoptosis of myocardial cells was evaluated by TUNEL assay. Results Compared with control group, the activity of CK, LDH and Caspase-3, the expression of Bax protein and the apoptosis rate of myocardial cells were significantly higher (P<0.01), and the activity of HO-1 activity as well as the expression of HO-1 and Bcl-2 protein were significantly lower in DOX group (P<0.01). Compared with DOX group, the activity of CK, LDH and Caspase-3, the expression of Bax protein and the apoptosis rate of myocardial cells were significantly lower (P<0.01), and the activity of HO-1 and the expression of HO-1 and Bcl-2 protein were significantly higher in DOX+RES group (P<0.01). Compared with DOX-RES group, the activity of CK, LDH and Caspase-3, the expression of Bax protein and the apoptosis rate of myocardial cells were significantly higher (P<0.01), and the activity of HO-1 and the expression of HO-1 and Bcl-2 protein were significantly lower in DOX＋RES+ ZnPP group (P<0.05). Conclusion HO-1 participates in the inhibition effect of RES on myocardial apoptosis induced by DOX.

Key words: doxorubicin, cardiotoxicity, apoptosis, resveratrol, heme oxygenase-1