Ischemia and reperfusion events, such as myocardial infarction (MI), are reported to induce remote organ damage severely compromising patient outcomes. Tissue survival and functional restoration relies on the activation of endogenous redox regulatory systems such as the oxidoreductases of the thioredoxin (Trx) family. Trxs and peroxiredoxins (Prxs) are essential for the redox regulation of protein thiol groups and for the reduction of hydrogen peroxide, respectively. Here, we determined whether experimental MI induces changes in Trxs and Prxs in the heart as well as in secondary organs. Levels and localization of Trx1, TrxR1, Trx2, Prx1, and Prx2 were analyzed in the femur, vertebrae, and kidneys of rats following MI or sham surgery. Trx1 levels were significantly increased in the heart (P = 0.0017) and femur (P < 0.0001) of MI animals. In the femur and lumbar vertebrae, Trx1 upregulation was detected in bone-lining cells, osteoblasts, megakaryocytes, and other hematopoietic cells. Serum levels of Trx1 increased significantly 2 days after MI compared to sham animals (P = 0.0085). Differential regulation of Trx1 in the bone was also detected by immunohistochemistry 1 month after MI. N-Acetyl-cysteine treatment over a period of 1 month induced a significant reduction of Trx1 levels in the bone of MI rats compared to sham and to MI vehicle. This study provides first evidence that MI induces remote organ upregulation of the redox protein Trx1 in the bone, as a response to ischemia–reperfusion injury in the heart.

据报道，缺血和再灌注事件，例如心肌梗塞（MI），会诱发远端器官损伤，严重损害患者预后。组织的存活和功能恢复依赖于内源性氧化还原调节系统的激活，例如硫氧还蛋白（Trx）家族的氧化还原酶。Trx和Peroxiredoxins（Prxs）分别对于蛋白质硫醇基的氧化还原调节和过氧化氢的还原至关重要。在这里，我们确定实验性MI是否在心脏以及次级器官中诱导Trxs和Prxs的变化。在MI或假手术后的大鼠的股骨，椎骨和肾脏中分析Trx1，TrxR1，Trx2，Prx1和Prx2的水平和位置。心脏中Trx1水平显着升高（P = 0.0017）和 MI动物的股骨（P <0.0001）。在股骨和腰椎中，在骨衬细胞，成骨细胞，巨核细胞和其他造血细胞中检测到Trx1上调。与假手术动物相比，MI后2天血清Trx1水平显着增加（P  = 0.0085）。MI后1个月也通过免疫组织化学检测到骨骼中Trx1的差异调节。与假手术和MI媒介物相比，N-乙酰半胱氨酸治疗1个月可显着降低MI大鼠骨骼中的Trx1水平。这项研究提供了第一个证据，表明MI可以诱导骨骼中氧化还原蛋白Trx1的远端器官上调，作为对心脏缺血-再灌注损伤的反应。