Effect of Sinomenine on Oxidative Stress and Myocardial Fibrosis in Rats with Heart Failure by Regulating JAK2/STAT3/SOCS1 Signaling Pathway
WANG Xia
SUN Jian
YU Mingyan
ZHAO Zhiyuan
Abstract：Objective:To observe the effects of sinomenine(SIN)on oxidative stress and myocardial fibrosis in chronic heart failure(CHF)rats,and to explore its impact on Janus activated kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)/suppressor of cytokine signaling-1(SOCS1)signaling pathway.Methods:The CHF rat model was established by constricting abdominal aorta,and randomly grouped into model group,captopril group(6.75 mg/kg),SIN low-dose group(5 mg/kg),and SIN medium-dose group(10 mg/kg),SIN high-dose group(20 mg/kg),and another sham operation(Sham)group was set,with 12 rats per group.After 4 weeks of continuous treatment,the cardiac function of the rats was detected by echocardiography.The changes of myocardial tissue were observed by hematoxylin-eosin(HE)and Masson staining.Enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1),superoxide dismutase(SOD),interleukin-1β(IL-1β),malondialdehyde(MDA),lactate dehydrogenase(LDH)in myocardial tissue.Western Blot was performed to detect the protein expression levels of collagen Ⅰ and Ⅲ(COL-Ⅰ,COL-Ⅲ),JAK2,phosphorylation JAK2(p-JAK2),STAT3,phosphorylated STAT3(p-STAT3)and SOCS1.Results:Compared with the Sham group,the levels of left ventricular ejection fraction(LVEF),left ventricular fraction shortening(LVFS),and SOD in the model group decreased(P＜0.05),the levels of LVEDD,LVESD,TNF-α,MCP-1,IL-1β,LDH,MDA,and the protein expressions of COL-Ⅰ,COL-Ⅲ,p-JAK2,p-STAT3,and SOCS1 increased(P＜0.05),myocardial fibers were disordered and infiltrated with a large number of inflammatory cells.Compared with the model group,the levels of LVEF,LVFS,and SOD in the captopril group and SIN low,medium and high dose groups increased(P＜0.05),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),TNF-α,MCP-1,IL-1β,LDH,MDA,and COL-Ⅰ,COL-Ⅲ,p-JAK2,p-STAT3,and SOCS1 protein expression levels decreased(P＜0.05),myocardial fiber arrangement tended to be normal,and cell infiltration had improved.Conclusion:SIN can alleviate the oxidative stress injury in the myocardial tissue of CHF rats and reverse the process of myocardial fibrosis,which may be related to the inhibition of JAK2/STAT3/SOCS1 signaling pathway.
Keywords：chronic heart failuresinomenineJanus activated kinase 2signal transducer and activator of transcription 3myocardial fibrosissuppressor of cytokine signaling-1experimental study
Publication Date：2025-02-15
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 364-370 )