The Effects of Ophiopogonin D on Myocardial Inflammation and Cell Apoptosis in Chronic Heart Failure Rats by Regulating the AMPK/SIRT1/NF-κB Signaling Pathway

This study aims to explore the effects of OPD (ophiopogonin D) on myocardial inflammation and cell apoptosis in CHF (chronic heart failure) rats by regulating the AMPK (AMP activated protein kinase)/SIRT1 (sirtuin 1)/NF-κB (nuclear factor-κB) signaling pathway. CHF rat model was constructed. CHF rats were classified into CHF group, low (L-OPD), medium (M-OPD), high (H-OPD) dose ophiopogonin D groups, and high dose ophiopogonin D+AMPK inhibitor Compound C group (H-OPD+Compound C group) randomly, each group with 12 rats. In addition, 12 normal rats were randomly served as the control group (NC group). Cardiac function was detected by echocardiogra phy. ELISA was used to detect the levels of serum myocardial markers and inflammation-related factors in each group. HE staining was used to observe the pathological changes of myocardial tissue. TUNEL staining was used to observe the number of TUNEL positive cells, and the apoptosis rate was calculated. Western blot was used to detect the expres sion of AMPK/SIRT1/NF-κB signaling pathway, apoptosis and myocardial fibrosis related proteins in myocardial tissue of each group. Inflammatory cell infiltration, obvious injury and serious myocardial fibrosis were observed in the CHF group. The cardiac function indexes of LVEDD (left ventricular end-diastolic diameter) and LVESD (left ventricular end-systolic diameter) in the CHF group were higher than those in the NC group (P<0.05). The myocardial markers NT proBNP (N-terminal pro-B-type natriuretic peptide) and CK-MB (creatine kinase isoenzyme) in the CHF group were higher than those in the NC group (P<0.05), and the inflammatory factors IL-1β and IL-18 were higher than those in the NC group (P<0.05). Compared with the NC group, the apoptosis rate and the expression levels of p-NF-κB p65/NF-κB p65, Bax, collagen type Ⅰ and collagen type Ⅲ were significantly increased (P<0.05), and the cardiac function indexes LVEF (left ventricular ejection fraction) and LVFS (left ventricular fractional shortening) were significantly decreased (P<0.05) in the CHF group. The expression levels of p-AMPK/AMPK, SIRT1 and Bcl-2 in the CHF group were lower than those in NC group (P<0.05). In L-OPD, M-OPD and H-OPD groups, inflammatory cell infiltration, pathological damage and myocardial fibrosis were reduced, LVEDD and LVESD were lower than those in CHF group (P<0.05), and myocardial markers NT-proBNP and CK-MB were lower than those in CHF group (P<0.05). The inflammatory factors IL-1β and IL-18 in the L-OPD, M-OPD and H-OPD groups were lower than those in the CHF group (P<0.05), the apoptosis rate, the expression levels of p-NF-κB p65/NF-κB p65, Bax, collagen type Ⅰ and collagen type Ⅲ in the L OPD, M-OPD and H-OPD groups were lower than those in the CHF group (P<0.05), and the cardiac function indexes LVEF and LVFS were higher than those in the CHF group (P<0.05). The expression levels of p-AMPK/AMPK, SIRT1 and Bcl-2 in the L-OPD, M-OPD and H-OPD groups were higher than those in the CHF group (P<0.05). Compared with the H-OPD group, the H-OPD+Compound C group had significantly increased LVEDD and LVESD (P<0.05) and significantly increased NT-proBNP and CK-MB (P<0.05). The inflammatory factors IL-1β and IL-18 in the H OPD+Compound C group were higher than those in the H-OPD group (P<0.05). The apoptosis rate, the ratio of p-NF-κB p65/NF-κB p65, Bax, collagen type Ⅰ and collagen type Ⅲ in the H-OPD+Compound C group were higher than those in the H-OPD group (P<0.05). Compared with the H-OPD group, the LVEF and LVFS in the H-OPD+Compound C group were significantly decreased (P<0.05), and the expression levels of p-AMPK/AMPK, SIRT1 and Bcl-2 were signifi cantly decreased (P<0.05). OPD alleviates myocardial inflammation and inhibits cell apoptosis in CHF rats, which may be closely related to the regulation of AMPK/SIRT1/NF-κB signaling pathway.

CSTR: 32200.14.cjcb.2025.11.0011