Effect of Astragalus polysaccharide on LPS-induced cardiomyocyte apoptosis by inhibiting NF-κB and JNK signaling pathway / 中国药理学通报

ABSTRACT

Aim To study the effect of Astragalus polysaccharide (APS) on the apoptosis of cardiomyocytes induced by lipopolysaccharide (LPS) in mice and to explore its mechanism.Methods Kunming mice were treated with APS for 14 days,and intraperitoneal injection of LPS (10 mg · kg-1) was performed to establish cardiomyocyte apoptosis model in vivo,and H9c2 cells were pre-administered with APS.After 30 min,LPS (1 mg · L-1) was incubated for 24 hours to establish a model of cardiomyocyte apoptosis.Cardiac ejection fraction (EF) and left ventricular shortening score (FS) were measured using echocardiography in mice.TUNEL was carried to measure myocardial cell apoptosis.Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum levels of IL-1β,TNF-α.Western blot was used to detect the expression of JNK,NF-κB signaling pathway and Bcl-2 family and caspase-3 protein in vivo and in vitro.Results LPS could significantly inhibit the left ventricular systolic function in mice and promote myocardial cell apoptosis.The levels of IL-1β,TNF-α in serum,JNK,p-JNK,Bax,caspase-3 and the concentration of NF-κB in nucleus were all increased,while the level of Bcl-2 and the concentration of NF-κB,IκB-α in cytoplasm were reduced.APS could significantly inhibit left ventricular systolic weakening in LPS-induced mice and cut down the apoptosis of cardiomyocytes.The secretion of IL-1β,TNF-α decreased to varying degrees.The protein levels of p-JNK,Bax,caspase-3 in myocardium and NF-κB in nucleus were down-regulated,but those of Bcl-2 and NF-κB,IκB-α in cytoplasm were up-regulated,and JNK had no significant change in vivo and in vitro.Conclusion APS ameliorates the LPS-induced apoptosis of myocardial cells by inhibiting NF-κB and JNK signaling pathway in mice.