ABSTRACT
Herein, we examined the protective effect of metoprolol combined with atractylenolide I (Atr I) in acute myocardial infarction (AMI) by regulating the SIRT3 (silent information regulator 3)/β-catenin/peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway. Briefly, 50 rats were randomly divided into the sham operation, model, metoprolol, Atr I, and combination metoprolol with Atr I groups (combined treatment group). The AMI model was established by ligating the left anterior descending coronary artery. After treatment, infarct size, histopathological changes, and cell apoptosis were examined using 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, and the TUNEL assay. The left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and left ventricular mass index (LVMI) were detected by echocardiography. Endothelin-1 (ET-1), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were detected using enzyme-linked immunosorbent assays. Furthermore, we measured lactate dehydrogenase (LDH), creatine kinase (CK) isoenzyme (CK-MB), and CK levels. Western blotting was performed to determine the expression of SIRT3, β-catenin, and PPAR-γ. Herein, the combined treatment group exhibited increased levels of LVEF, LVFS, and NO, whereas LVMI, ET-1, TNF-α, IL-6, LDH, CK-MB, and CK levels were decreased. Importantly, the underlying mechanism may afford protection against AMI by increasing the expression levels of SIRT3, β-catenin, and PPAR-γ.
KEYWORDS:
Acute myocardial infarction; Metoprolol; Atractylenolide I; SIRT3/β-Catenin/PPAR-γ pathway
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**p 0.01 or # p<0.05, ## p<0.01 compared with the sham-operated group or AMI group, a p<0.05 or b p<0.05 compared with the metoprolol or Atr I group. AMI, acute myocardial infarction; Atr I, atractylenolide I; LVEF, left ventricular ejection fraction; LVFS, left ventricular fraction shortening; LVMI, left ventricular mass index.
**p<0.01 or # p<0.05, ## p<0.01 compared with the sham-operated group or AMI group, a p<0.05 or b p<0.05 compared with the metoprolol or Atr I group. AMI, acute myocardial infarction; Atr I, atractylenolide I; ET-1, endothelin-1; IL-6, interleukin-6; NO, nitric oxide; TNF-α, tumor necrosis factor-α.
**p<0.01 or # p<0.05, ## p<0.01 compared with the sham-operated group or AMI group, a p<0.05 or b p<0.05 compared with the metoprolol or Atr I group. AMI, acute myocardial infarction; Atr I, atractylenolide I; CK, creatine kinase; CK-MB, creatine kinase isoenzyme LDH, lactate dehydrogenase.
**p<0.01 or # p<0.05, ## p<0.01 compared with the sham-operated group or AMI group, a p<0.05 or b p<0.05 compared with the metoprolol or Atr I group. AMI, acute myocardial infarction; Atr I, atractylenolide I; PPAR-γ, proliferator-activated receptor gamma; SIRT3, silent information regulator 3.