Effects of Hesperetin on Cardiac Function and Myocardial Fibrosis in Rats with Chronic Heart Failure by Regulating Notch/Hes-1 Signaling Pathway

This study aims to explore the effects of HSP (hesperetin) on cardiac function and myocardial fibrosis in rats with CHF (chronic heart failure) by regulating the Notch/Hes-1 (hairy and enhancer of split homolog 1) signaling pathway. A CHF rat model was constructed, and successfully modeled rats were randomly separated into CHF group, HSP low-dose group (HSP-L group), HSP medium-dose group (HSP-M group), HSP high-dose group (HSP-H group), and HSP high-dose+Hotch/Hes-1 signaling pathway inhibitor DAPT group (DAPT group), with 15 rats in each group. Another 15 normal rats were randomly selected as the Con group. The ultrasonic imaging system for small animals was used to detect the cardiac function parameters of each group of rats. ELISA was used to measure serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) and myocardial enzymes; the cardiac mass index and left ventricular mass index of rats in each group were also measured. HE and Masson staining were used to observe the morphological changes and fibrosis in the myocardial tissues of each group of rats. The content of HYP (hydroxyproline) in myocardial tissue was detected by HYP test box. Immunohistochemistry and Western blot were used to detect myocardial fibrosis and Notch/Hes-1 signaling pathway-related protein expression. Compared with the Con group, the CHF group showed severe damage to the myocardial tissue structure, and structural disorder, rupture and focal dissolution of myocardial fibers were observed. The LVEF (left ventricular ejection fraction), LVFS (left ventricular fractional shortening), the Notch1 and Hes-1 expression levels reduced, while the NT-proBNP, CK (creatine kinase), CK-MB (creatine kinase isoenzyme), cardiac mass index, left ventricular mass index, CVF (collagen volume fraction), HYP content, α-SMA (α-smooth muscle actin) fluorescence intensity, and ColⅠ (collagen Ⅰ) and ColⅢ (collagen Ⅲ) expression levels elevated (P<0.05). Compared with the CHF group, the HSP-L group, HSP-M group, and HSPH group showed improvement in myocardial tissue structure damage and collagen fiber deposition, the LVEF, LVFS, and the Notch1 and Hes-1 expression levels elevated, while the NT-proBNP, CK, CK-MB, cardiac mass index, left ventricular mass index, CVF, HYP content, α-SMA fluorescence intensity, and the ColⅠ and ColⅢ expression levels reduced (P<0.05). Compared with the HSP-H group, the DAPT group showed aggravated myocardial tissue structural damage and fibrosis, the LVEF, LVFS, and the Notch1 and Hes-1 expression levels reduced, while the NT-proBNP, CK, CK-MB, cardiac mass index, left ventricular mass index, CVF, HYP content, α-SMA fluorescence intensity, and the ColⅠ and ColⅢ expression levels elevated (P<0.05). HSP can improve cardiac function and myocardial fibrosis in CHF rats, which may be related to the activation of the Notch/Hes-1 signaling pathway.

CSTR: 32200.14.cjcb.2026.02.0014