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<p>Myocardial cell injury following myocardial infarction (MI) is closely associated with abnormal glycolysis metabolism. Shexiang-Tongxin Dropping Pill (STDP) exhibits potential cardioprotective effects, but its mechanism in regulating post-MI glycolysis remains poorly understood. This study aimed to elucidate the molecular mechanism by which STDP ameliorates MI-induced injury through integrin subunit beta 2 (ITGB2) methylation regulation, providing new therapeutic insights and potential targets. The in vivo MI model was generated by permanent ligation of the left anterior descending coronary artery in Sprague-Dawley rats, while the in vitro model was established through hypoxia/reoxygenation treatment in AC16 cardiomyocytes. Histopathological evaluation of myocardial injury and apoptosis was performed using hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, respectively. Cardiac functional impairment was quantified by measuring serum lactate dehydrogenase (LDH) and creatine kinase-myocardial band (CK-MB) levels. Western blot analysis was conducted to examine the expression of fibrosis-related proteins (collagen I, α-smooth muscle actin) and cardiac remodeling markers (atrial natriuretic peptide, brain natriuretic peptide). Cellular glycolytic metabolism was assessed by monitoring extracellular acidification rate and oxygen consumption rate using Seahorse metabolic analysis. Furthermore, methylation-specific PCR (MSP) combined with DNA immunoprecipitation was employed to investigate ITGB2 promoter methylation status. STDP significantly attenuated myocardial fibrosis, apoptosis, and cardiac dysfunction in MI rats, concurrently reducing serum LDH and CK-MB levels. It suppressed glycolytic activity and the expression of pyruvate kinase M2 (PKM2). Furthermore, STDP upregulated ITGB2 promoter methylation and decreased its expression. These protective effects were reversed by the methylation inhibitor 5-aza-2’-deoxycytidine. STDP promotes ITGB2 promoter methylation, thereby reducing its expression. This process is associated with the restoration of abnormal glycolysis and downregulation of PKM2, collectively contributing to the amelioration of myocardial injury post-MI.</p>

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Shexiang Tongxin dropping pills attenuate cardiac remodeling in myocardial infarction rats by inhibiting Glycolysis via ITGB2 methylation

  • 期刊论文

  • 发表日期：

    2026年3月7日

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  • XinYuan Xu,
  • Ling Sun,
  • Hao Zhang,
  • HaiHua Pan,
  • ChangLin Zhai

摘要

Myocardial cell injury following myocardial infarction (MI) is closely associated with abnormal glycolysis metabolism. Shexiang-Tongxin Dropping Pill (STDP) exhibits potential cardioprotective effects, but its mechanism in regulating post-MI glycolysis remains poorly understood. This study aimed to elucidate the molecular mechanism by which STDP ameliorates MI-induced injury through integrin subunit beta 2 (ITGB2) methylation regulation, providing new therapeutic insights and potential targets. The in vivo MI model was generated by permanent ligation of the left anterior descending coronary artery in Sprague-Dawley rats, while the in vitro model was established through hypoxia/reoxygenation treatment in AC16 cardiomyocytes. Histopathological evaluation of myocardial injury and apoptosis was performed using hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, respectively. Cardiac functional impairment was quantified by measuring serum lactate dehydrogenase (LDH) and creatine kinase-myocardial band (CK-MB) levels. Western blot analysis was conducted to examine the expression of fibrosis-related proteins (collagen I, α-smooth muscle actin) and cardiac remodeling markers (atrial natriuretic peptide, brain natriuretic peptide). Cellular glycolytic metabolism was assessed by monitoring extracellular acidification rate and oxygen consumption rate using Seahorse metabolic analysis. Furthermore, methylation-specific PCR (MSP) combined with DNA immunoprecipitation was employed to investigate ITGB2 promoter methylation status. STDP significantly attenuated myocardial fibrosis, apoptosis, and cardiac dysfunction in MI rats, concurrently reducing serum LDH and CK-MB levels. It suppressed glycolytic activity and the expression of pyruvate kinase M2 (PKM2). Furthermore, STDP upregulated ITGB2 promoter methylation and decreased its expression. These protective effects were reversed by the methylation inhibitor 5-aza-2’-deoxycytidine. STDP promotes ITGB2 promoter methylation, thereby reducing its expression. This process is associated with the restoration of abnormal glycolysis and downregulation of PKM2, collectively contributing to the amelioration of myocardial injury post-MI.