Delivery of astragalus polysaccharide by ultrasound microbubbles attenuate doxorubicin-induced cardiomyopathy in rodent animals

The aim of this study was to investigate the cardioprotective effects and probable mechanism of ultrasound-targeted microbubble destruction (UTMD) combined with astragalus polysaccharide (APS) on diabetic cardiomyopathy (DCM) model rats. The DCM rats with diabetes and cardiomyopathy were induced via chronic treatment of doxorubicin and then randomly divided into the (1) DCM model group; (2) APS microbubble group; (3) UTMDgroup; and (4) APS microbubbles combined with UTMD group. After 4-week intervention, the fasting blood glucose levels, body weight, %HbA1c level and glucose tolerance of DCM rats received combination therapy were significantly improved as compared with those of UTMD or saline-treated ones. Moreover, the heart/body weight ratio, and myocardial contractility were all improved after receiving combination therapy groups compared with others. In addition, significantly upregulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as significantly downregulated malondialdehyde (MDA) levels were all observed in the ones received combined treatment compared to others. Furthermore, the lipid accumulation and the expression levels of inflammatory factors were all significantly down-regulated in those ones received combination therapy compared with others (all P < 0.05). Further pathological analysis demonstrated that combination therapy effectively ameliorated fibrosis and myocardial morphological changes of DCM rats via activating the upregulation of AMPK and PPAR-γ signaling pathway, and inhibiting NF-κB activity in myocardial tissues of DCM rats. In conclusion, APS microbubbles combined with UTMD effectively protect the myocardial injury of DCM rats via activating AMPK signaling pathway to alleviate inflammation response, fibrosis and oxidative stress in myocardial tissues.