Fuling Sini Decoction Inhibits TLR4/NF-κB Pathway and Improves Cardiac Function in Rats with Chronic Heart Failure
ZHANG Meng, et al
Hubei University of Chinese Medicine / Wuhan Central Hospital,Tongji Medical College,Huazhong University of Science and Technology, Hubei Wuhan 430000, China
Abstract:Objective: To investigate the influences of Fuling Sini Decoction on cardiac function in rats with chronic heart failure and the possible molecular mechanism. Methods: The rat model of chronic heart failure was established using intraperitoneal injection of doxorubicin.Rats that were successfully modeled were randomly divided into the model group,low,medium,and high-dose Fuling Sini Decoction groups (6 g/kg,12 g/kg,18 g/kg),and a captopril group (2.25mg/kg),with 12 rats in each group.An additional 12 rats were intraperitoneally injected with normal saline as the control group.Cardiac function indicators were assessed using echocardiography; serum levels of tumor necrosis factor-α (TNF-α),interleukin (IL)-1β,and IL-6 were measured using ELISA; myocardial tissue histopathological changes were observed using HE staining; cardiomyocyte apoptosis rates were determined through TUNEL staining; Western blot was employed to measure the expression levels of Toll-like receptor 4 (TLR4),nuclear factor-κB (NF-κB),p-NF-κB,nuclear factor κB inhibitory protein α (IκBα),and p-IκBα proteins in myocardial tissue. Results: Compared to the control group,rats in the model group exhibited increased left ventricular ejection fraction (LVEF) and left ventricular short-axis shortening rate (LVFS) (P<0.05),as well as increased left ventricular end-systolic diameter (LVESD),left ventricular end-diastolic diameter (LVEDD),serum levels of TNF-α,IL-1β,and IL-6.The degree of myocardial tissue pathological injury worsened,and there was an increase in cardiomyocyte apoptosis rates and the expression levels of TLR4,p-NF-κB/NF-κB,and p-IκBα/IκBα proteins in myocardial tissue (P<0.05).Compared to the model group,rats in the low,medium,and high-dose Fuling Sini Decoction groups and the captopril group exhibited increased LVEF and LVFS (P<0.05),decreased LVESD,LVEDD,serum TNF-α,IL-1β,and IL-6 levels,and reduced pathological damage in myocardial tissue.There was also a decrease in cardiomyocyte apoptosis rates and the expression levels of TLR4,p-NF-κB/NF-κB,and p-IκBα/IκBα proteins in myocardial tissue (P<0.05). Conclusion: Fuling Sini Decoction can inhibit the activation of the TLR4/NF-κB pathway,reduce myocardial damage,and improve cardiac function in rats with chronic heart failure.
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