Thiazolidinediones are insulin-sensitizing drugs, ligands for peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which play an important role in the modulation of inflammatory responses. Myocardial ischemia/reperfusion (MI/R) injury is associated with inflammation, in which various cells, particularly monocytes and macrophages, are involved. This study examined the effects of the thiazolidinedione peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, in a rat model of MI/R injury. Pioglitazone at 3 mg/kg/day or the vehicle was administered for 7 days before rats were subjected to 30 minutes of coronary ligation followed by 24 hours of reperfusion. The mRNA expression [monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1] in the ischemic region, the number of infiltrating macrophages in the ischemic region, and the myocardial infarct size were examined. The inhibitory effects of pioglitazone on activated macrophages were studied in vitro. Phorbol 12-myristate 13-acetate-induced MCP-1 production, in the absence or presence of pioglitazone, were assayed in cultured macrophages. Compared with the control group, (1). mRNA levels of MCP-1 and intercellular adhesion molecule-1 and the number of infiltrating macrophages in the ischemic region were significantly lower in the pioglitazone-treated group; and (2). myocardial infarct size was significantly smaller in the pioglitazone-treated group. Phorbol 12-myristate 13-acetate-stimulated cultured macrophages in the presence of pioglitazone produced significantly lower levels of MCP-1 than the stimulated control in the absence of pioglitazone. These observations demonstrate that pioglitazone has anti-inflammatory effects in MI/R injury that are independent of its insulin-sensitizing effect.

中文翻译：

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吡格列酮是一种过氧化物酶体增殖物激活受体-γ 激动剂，可减轻大鼠模型中的心肌缺血/再灌注损伤。

噻唑烷二酮类药物是胰岛素增敏药物，是过氧化物酶体增殖物激活受体-γ (PPAR-γ) 的配体，在调节炎症反应中发挥重要作用。心肌缺血/再灌注 (MI/R) 损伤与炎症有关，炎症涉及多种细胞，尤其是单核细胞和巨噬细胞。本研究检查了噻唑烷二酮过氧化物酶体增殖物激活受体-γ 配体吡格列酮在 MI/R 损伤大鼠模型中的作用。吡格列酮以 3 mg/kg/天或载体给药 7 天，然后对大鼠进行 30 分钟的冠状动脉结扎，然后进行 24 小时的再灌注。缺血区mRNA[单核细胞趋化蛋白-1（MCP-1）和细胞间粘附分子-1]的表达，检查缺血区域浸润巨噬细胞的数量和心肌梗塞面积。在体外研究了吡格列酮对活化的巨噬细胞的抑制作用。在不存在或存在吡格列酮的情况下，在培养的巨噬细胞中测定了佛波醇 12-肉豆蔻酸酯 13-乙酸酯诱导的 MCP-1 产生。与对照组相比，(1)。吡格列酮治疗组MCP-1和细胞间粘附分子-1的mRNA水平和缺血区浸润巨噬细胞的数量显着降低；和（2）。吡格列酮治疗组的心肌梗塞面积明显较小。在吡格列酮存在下，佛波醇 12-肉豆蔻酸酯 13-乙酸酯刺激培养的巨噬细胞产生的 MCP-1 水平显着低于没有吡格列酮的刺激对照。