Acute myocardial infarction (AMI) has been a devastating actuality and accounts for half of cardiovascular emergency department visits. Nucleotide oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome participates in the mediation of myocardial inflammation during AMI. Therefore, this study aimed to reveal the therapeutic function of tranilast, an agent targeting NLRP3, for AMI. AMI mouse model was first established by transient myocardial ischemia. Western blot and quantitative reverse transcription polymerase chain reaction assay were performed to estimate the expression levels of related genes. Flow cytometry was used to analyze the macrophage types, and the therapeutic effects of tranilast were estimated by echocardiographic analysis and Masson's trichrome stain. We demonstrated that AMI induced the activation of NLRP3 inflammasome in the heart tissues of mice with AMI. Tranilast decreased the expression of interleukin-1β and cleaved caspase-1 in bone marrow-derived macrophages and thus re-educated M1-macrophages toward the M2-phenotype both in vitro and in vivo. Tranilast inhibited the activation in the heart tissues of AMI mice and thus improved cardiac functional recovery in the AMI mouse model. In conclusion, we revealed that tranilast ameliorated myocardial infarction by inhibiting NLRP3 inflammasome and re-educating macrophage phenotype in this study.

中文翻译：

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曲尼司特对心肌梗死小鼠模型炎症小体和巨噬细胞表型的影响


急性心肌梗塞 (AMI) 是一种毁灭性的现实，占心血管急诊就诊人数的一半。核苷酸寡聚化结构域、富含亮氨酸的重复序列和含有热蛋白结构域的蛋白 3 (NLRP3) 炎症小体参与 AMI 期间心肌炎症的介导。因此，本研究旨在揭示NLRP3靶向药物曲尼司特对AMI的治疗作用。 AMI小鼠模型首先通过短暂性心肌缺血建立。进行蛋白质印迹和定量逆转录聚合酶链反应测定来估计相关基因的表达水平。采用流式细胞术分析巨噬细胞类型，并通过超声心动图分析和Masson三色染色评估曲尼司特的治疗效果。我们证明，AMI 诱导 AMI 小鼠心脏组织中 NLRP3 炎症小体的激活。曲尼司特降低了骨髓源性巨噬细胞中白细胞介素-1β和裂解的 caspase-1的表达，从而在体外和体内将 M1 巨噬细胞重新教育为 M2 表型。曲尼司特抑制 AMI 小鼠心脏组织的活化，从而改善 AMI 小鼠模型的心脏功能恢复。总之，我们在本研究中发现曲尼司特通过抑制 NLRP3 炎性体和重新教育巨噬细胞表型来改善心肌梗死。