The Effect of Dapagliflozin on Chronic Heart Failure in Rats through Regulation of the miR-20a-5p/CCND2 Axis
HAN Qing
LIU Xiaojuan
REN Xiaoqian
QIU Yi
LIU Xue
XING Jinmei
Abstract：Objective:To explore the effect of Dapagliflozin(DAPA)on chronic heart failure(CHF)in rats by regulating the microRNA-20a-5p(miR-20a-5p)/cyclin D2(CCND2)axis.Methods:CHF rat models were established and divided into the following groups:sham surgery group(Sham group),model group(CHF group),low-dose Dapagliflozin group(DAPA-L group),high-dose Dapagliflozin group(DAPA-H group),high-dose Dapagliflozin+miR-20a-5p agonist negative control group(DAPA-H+agomir-NC group),and high-dose Dapagliflozin+miR-20a-5p agonist group(DAPA-H+miR-20a-5p agomir group).Echocardiography was applied to evaluate cardiac function.Enzyme linked immunosorbent assay(ELISA)was applied to detect levels of interleukin-6(IL-6),tumor necrosis factor α(TNF-α),and interleukin-1β(IL-1β).Terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)was applied to detect cell apoptosis.Hematoxylin and eosin(HE)staining was applied to observe the morphology of myocardial tissue.Masson's staining was applied to evaluate the degree of myocardial tissue fibrosis.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression levels of miR-20a-5p and CCND2.Western blot was used to detect the levels of Cleaved Caspase-3,Bax,Bcl-2,and CCND2 proteins.Results:Compared with the Sham group,some myocardial cells in the CHF group were necrotic,and structurally disordered.Myocardial cells were swollen,with large number of inflammatory cells infiltration.The levels of left ventricular diastolic pressure(LVDP),IL-6,TNF-α,and IL-1β,as well as the cell apoptosis rate,collagen composition,fibrosis,Cleaved Caspase-3,Bax expression,and miR-20a-5p expression increased significantly(P＜0.05).In contrast,the levels of left ventricular systolic pressure(LVSP)and left ventricular ejection fraction(LVEF),along with the expression levels of Bcl-2 and CCND2,decreased significantly(P＜0.05).Compared with the CHF group,the arrangement of myocardial fibers in the DAPA-L group and DAPA-H group was regular,and the swelling,necrosis,and inflammatory cell infiltration of myocardial cells reduced.The levels of LVDP,IL-6,TNF-α,and IL-1β,as well as the cell apoptosis rate,collagen composition,fibrosis,Cleaved Caspase-3,Bax,and miR-20a-5p expression levels,significantly decreased(P＜0.05).Meanwhile,the levels of LVSP and LVEF,and the expression levels of Bcl-2 and CCND2 significantly increased(P＜0.05).Compared with the DAPA-H+agomir-NC group,the DAPA-H+miR-20a-5p-agomir group showed increase of swelling,necrosis,and inflammatory cell infiltration of myocardial cells.The arrangement of myocardial fibers was disordered.The levels of LVDP,IL-6,TNF-α,and IL-1β,cell apoptosis rate,collagen composition and fibrosis,and the expression levels of Cleaved Caspase-3,Bax,and miR-20a-5p significantly increased(P＜0.05).In contrast,the levels of LVSP and LVEF,as well as the expression levels of Bcl-2 and CCND2,significantly reduced(P＜0.05).Conclusion:Dapagliflozin can improve heart function in rats with by down-regulating the expression of miR-20a-5p and promoting the expression of CCND2.
Keywords：chronic heart failureDapagliflozinmicroRNA-20a-5pcyclin-D2experiment study
Publication Date：2025-08-10
Online Publishing Date：2025-08-20(First online date of this platform, not the publication date of the document)
Pages：9( 2298-2306 )