The common mechanism underlying Shuangxinfang's amelioration of post-myocardial infarction depression: Targeting S100A9/NLRP3 to improve mitochondrial energetics

作者：Ding W, Shao J, Zhao W, Hou J, Zhang Y, Sun Z, Liu X, Wang J, Wang C, Zhao H · 发表于：Phytomedicine : international journal of phytotherapy and phytopharmacology · 年份：2026 · DOI：10.1016/j.phymed.2026.158477 · 研究领域：Drugs, Chinese Herbal、Myocardial Infarction、Calgranulin B、NLR Family, Pyrin Domain-Containing 3 Protein、Depression、Mitochondria、Animals、Rats、Male、Rats, Sprague-Dawley、Myocytes, Cardiac、Energy Metabolism

BACKGROUND: Post-myocardial infarction (post-MI) depression is a common clinical complication affecting approximately 29-40% of post-MI patients, whose pathological mechanism remains incompletely understood. While Shuangxinfang (Psycho-cardiology formula, PCF) has demonstrated efficacy in treating post-MI depression, its specific underlying mechanism of action remains poorly understood. OBJECTIVE: This study seeks to elucidate the common pathological mechanisms underlying myocardial infarction and depression, as well as the therapeutic pathway by which PCF exerts its effects, through an integrated approach combining transcriptomics, cellular experiments, and animal studies. METHOD: Transcriptomic analysis was employed to identify the potential molecular pathways. Cellular models employing H9C2 cardiomyocytes and astrocytes were established and subjected to hypoxia/reoxygenation intervention and S100A9 overexpression plasmid transfection, respectively. A rat model of post-MI depression was established. To validate the key findings, the following analytical methods were employed in the present study: real-time quantitative PCR (qRT-PCR), Western blotting, immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), colorimetric assays, and transmission electron microscopy (TEM). RESULTS: Transcriptomic analysis revealed that PCF potentially targets S100A9, the NLRP3 inflammasome, and mitochondrial dysfunction. Both in viv...