Shenfu Injection regulates macrophage polarization via TLR4/NF-κB pathway to reduce inflammation in chronic heart failure
This study aimed to investigate the therapeutic effect of Shenfu Injection on mice with chronic heart failure(CHF)and its effect on macrophage polarization.C57BL/6J mice were randomly assigned to the normal and model groups.The CHF model was es-tablished by intraperitoneal injection of isoproterenol(ISO,7.5 mg·kg-1,28 d).The successful modeling was determined by asses-sing the cardiac function and N-terminal pro-brain natriuretic peptide(NT-proBNP).The modeled mice were randomly divided into the model group,Shenfu Injection group,and TAK-242 group,and were injected intraperitoneally with the corresponding drugs for 15 days.Cardiac function was evaluated using echocardiography.Hematoxylin-eosin(HE)staining was used to detect the pathomorpholo-gy.Enzyme-linked immunosorbent assay(ELISA)was used to detect the values of serum NT-proBNP,interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-10,and arginase 1(Arg-1).Flow cytometry was applied to detect the relative content and M1/M2 po-larization of cardiac macrophages.Quantitative polymerase chain reaction(qPCR)and Western blot were used to detect the changes in the Toll-like receptor 4(TLR4)/nuclear factor-KB(NF-κB)pathway-related mRNA and protein expressions.Compared with the nor-mal group,mice in the model group had lower values of left ventricular ejection fraction(LVEF)and left ventricular fractional shorte-ning(LVFS),higher values of left ventricular internal diastolic end-diastolic(LVIDd),left ventricular internal diastolic end-systolic(LVIDs),NT-proBNP,TNF-α,and IL-6(P＜0.01);the number of macrophages increased in cardiac tissues(P＜0.05),and the values of M1-F4/80+CD86+were increased(P＜0.01),while the values of M2-F4/80+CD163+decreased(P＜0.05);the mRNA and protein expressions of TLR4,myeloid differentiation factor 88(MyD88),IκB kinase α(IKKα),and NF-κB p65 in myocardial tissues were significantly elevated(P＜0.05,P＜0.01).Compared with the model group,mice in the Shenfu Injection and TAK-242 groups showed elevated LVEF,LVFS,IL-10,and Arg-1 levels,and decreased LVIDd,LVIDs,NT-proBNP,TNF-α,and IL-6 levels(P＜0.05,P＜0.01);the cardiac F4/80+CD11b+(macrophage)and M1-F4/80+CD86+values were significantly down-regulated,while M2-F4/80+CD163+values were increased(P＜0.05,P＜0.01);and the mRNA and protein expressions of TLR4,MyD88,IKKα,and NF-κB p65 in myocardial tissues were notably decreased(P＜0.05,P＜0.01).CHF mice have an imbalance of M1/M2 macrophage polarization,with M1-type macrophages predominating.Shenfu Injection promotes macrophage polarization towards M2,inhibits M1-type macrophage activation,and attenuates inflammatory responses in heart failure by regulating the TLR4/NF-κB signaling pathway.
NETL
NSTL
万方数据
