Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (12): 13-18.doi: 10.6040/j.issn.1671-7554.0.2022.0564

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Effects of tolvaptan combined with dapagliflozin on myocardial fibrosis in rats with heart failure

GAO Yan1, ZHU Qingying2, LUAN Mingya1, LIU Kewei1   

  1. 1. Department of General Practice, The 960th Hospital of PLA, Jinan 250031, Shandong, China;
    2. School of Clinical Medicine, Weifang Medical University, Weifang 261053, Shandong, China
  • Published:2022-12-01

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Abstract: Objective To assess the effects of tolvaptan(TLV)and dapagliflozin(DAPA)alone and in combination on the myocardial fibrosis and transforming growth factor-β1(TGF-β1)expression in rats with chronic heart failure. Methods Male Wistar rats were randomly divided into control group, model group, TLV-L group, TLV-H group, DAPA group and TLV-H+DAPA group. Except for the control group, rats in the other groups were given intraperitoneal injection of adriamycin 3 mg/kg once a week for 6 weeks for modeling. After cardiac ultrasound examination of EF<60% indicated successful modeling of heart failure, the rats were randomized into groups and received pharmacological intervention for 30 days. The morphological changes of heart tissue were observed with hematoxylin-eosin(HE)staining; the degree of myocardial fibrosis was detected with Masson staining; the collagen volume fraction(CVF)was calculated; the apoptotic index of myocardial cells was detected with TUNEL staining; the protein expressions of TGF-β1, p-Smad2 and p-Smad3 in the left ventricular myocardial tissue were detected with Western blotting. Results Compared with the control group, the model group showed disordered arrangement of myocardial fibers, more infiltrated inflammatory cells, significant myocardial fibrosis, increased apoptosis, significantly higher protein expression of TGF-β1, and decreased protein expressions of p-Smad2 and p-Smad3(P<0.05). Compared with the model group, the TLV group, DAPA group and TLV-H+DAPA group had significantly reduced myocardial fibrosis and myocardial apoptosis index(P<0.05), significantly reduced protein expression of TGF-β1, and significantly increased protein expressions of p-Smad2 and p-Smad3(P<0.05). Conclusion TLV and DAPA alone and in combination can inhibit myocardial fibrosis by inhibiting the TGF-β1/Smad2/3 signaling pathway, and the effect of combined use is better than that of single drug.

Key words: Tolvaptan, Dapagliflozin, Chronic heart failure, Myocardial fibrosis, Transforming growth factor-β1

CLC Number: 

  • R542.2
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