Qiliqiangxin improves cardiac function and attenuates cardiac remodelling in doxorubicin-induced heart failure rats

摘要

Context: Therapeutic doxorubicin administration is restricted as this anticancer drug may be cardiotoxic. The traditional Chinese medicine qiliqiangxin has been approved for clinical treatment of chronic heart failure. Objective: To explore the protective effects and molecular mechanisms of qiliqiangxin on doxorubicin-induced congestive heart failure (CHF) in rats. Materials and methods: A CHF rat model was established via intraperitoneal DOX injections (2.5?mg/kg/week) for 6 weeks. The rats were randomly assigned to control, CHF, CHF?+?QL (1.0?g/kg/d), or captopril (3.8?mg/kg/d) treatment groups (n?=?10) for 4 weeks. MicroRNA sequencing elucidated the molecular mechanisms of qiliqiangxin on doxorubicin-induced CHF in rats. Results: Unlike in the CHF group, QL significantly reduced Bax:Bcl-2 (2.05?±?0.23 vs. 0.94?±?0.09, p??0.05) and the levels of collagen I (0.19?±?0.02 vs. 0.15?±?0.01, p??0.05), collagen III (0.19?±?0.02 vs. 0.14?±?0.02, p??0.05), TGF-β1 (5.28?±?0.89 vs. 2.47?±?0.51, p??0.05), Smad3 (1.23?±?0.12 vs. 0.78?±?0.09, p??0.05), MMP-2 (0.89?±?0.01 vs. 0.53?±?0.05, p??0.05), and TIMP-2 (0.24?±?0.03 vs. 0.44?±?0.03, p??0.05). QL also upregulated TGF-β3 (0.65?±?0.06 vs. 0.96?±?0.10, p??0.05) and Smad7 (0.09?±?0.01 vs. 0.19?±?0.023, p??0.05). Moreover, Smad3 was a target of miR-345-3p. Discussion and Conclusions: The beneficial effects of QL on DOX-induced CHF in rats are mediated by reduction in myocardial fibrosis, promotion of TGF-β3/Smad7, and inhibition of TGF-β1/Smad3. QL may also modulate specific miRNAs. These results provide evidence that QL might be an effective treatment for DOX-induced CHF.