Xutao Sun1, Guozhen Chen2, Ying Xie1, Deyou Jiang1, Jieru Han1, Fei Chen1, Yunjia Song1,3. 1. School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, P. R. China. 2. Department of Pediatrics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, P. R. China. 3. Peking University First Hospital, Beijing, P. R. China.
Abstract
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.
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.
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