Myocardial protection of propofol on apoptosis induced by anthracycline by PI3K/AKT/Bcl-2 pathway in rats

BACKGROUND: The release of proinflammatory cytokines is inhibited by propofol, which could reduce oxidative stress and suggests that propofol could ameliorate the adverse effects of anthracyclines in myocardial cells as a promising cardioprotective agent. The aim of the study was to evaluate the protective effects of propofol on phosphatidylinositol 3 kinase/protein kinase B/B cell lymphoma 2 (PI3K/AKT/Bcl-2) pathway in cardiomyocyte apoptosis induced by doxorubicin [adriamycin (ADM)] of rat cardiomyocytes in vivo. METHODS: The 40 F344 female rats were randomly divided into 4 groups (n=10): treatment control, ADM, Propofol (Prop) and ADM + Prop group. Blood samples were taken as baseline, before the 4th administration of the agents and before humane death. The serum levels of malondialdehyde (MDA), an oxidant factor, were detected by the thiobarbituric acid method. Superoxide dismutase (SOD) levels were analyzed by xanthine oxidase, and those of cardiac troponin I (cTnI), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were analyzed by enzyme linked immunosorbent assay (ELISA). Apoptosis of cardiac myocytes was measured by flow cytometry. The expression levels of PI3K-110α and pAKT-Ser473 and Bcl-2 proteins in rat heart tissue were detected by western blot. RESULTS: Apoptosis induced by ADM was significantly reduced by propofol. Compared with the ADM group, the serum levels of MDA, cTnI and BNP in the ADM + Prop group were significantly downregulated. In addition, the PI3K-110α and pAKT-Ser473 expressions in the ADM group were significantly higher than those in the ADM + Prop group, and the increases in Bcl-2 expression in the ADM + Prop group was statistically significant compared with the ADM group. CONCLUSIONS: We identified that the PI3K/AKT/Bcl-2 axis is involved in the regulation of cardiomyocyte apoptosis induced by ADM in vivo. In addition, our results elucidated that propofol had a protective role in cardiomyocyte apoptosis induced by ADM by suppressing the PI3K/AKT/Bcl-2 pathway.