Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Int Immunopharmacol. 2022 Nov;112:109208. doi: 10.1016/j.intimp.2022.109208. Epub 2022 Sep 7.
Pulmonary fibrosis is common in the development of inflammatory lung diseases with no effective clinical drug treatment currently. As an essential redox enzyme, thioredoxin (Trx) has been reported to be involved in pulmonary fibrosis, but the mechanism is to be revealed. Therefore, in bleomycin-indued pulmonary fibrosis model in C57 mice, Trx activity and nitrated Trx were examined.,p38-MAPK apoptosis pathway was determined in lung tissues. Additionally, before BLM administration, C57/BL6 mice were treated with aminoguanidine (AG, a peroxynitrite scavenger), recombinant human Trx-1 (rhTrx-1), or SIN-1 (a peroxynitrite donor) nitrated Trx-1 (N-Trx-1). In bleomycin (BLM)-induced pulmonary fibrosis model in C57/BL6 mice, we observed that nitrated Trx increased, while its activity decreased, with the increase of alveolar epithelial cells (AECs)apoptosis by p38-MAPK pathway. We demonstrated that AG or rhTrx-1, but not N-Trx-1 significantly reduced pulmonary fibrosis. Taken together, the results above revealed that blockade of Trx-1 nitration, or supplementation of exogenous rhTrx-1, might represent novel therapies to attenuate pulmonary fibrosis in idiopathic pulmonary fibrosis patients.
肺纤维化是炎症性肺部疾病发展中的常见病症，但目前尚无有效的临床药物治疗方法。硫氧还蛋白（Trx）作为一种重要的氧化还原酶，已被报道参与肺纤维化，但具体机制尚不清楚。因此，在 C57 小鼠博莱霉素诱导的肺纤维化模型中，我们检测了 Trx 活性和硝化 Trx 的变化，同时还研究了肺组织中 p38-MAPK 凋亡途径。此外，在给予博莱霉素之前，我们用氨基胍（AG，过氧亚硝酸盐清除剂）、重组人 Trx-1（rhTrx-1）或 SIN-1（过氧亚硝酸盐供体）预处理 C57/BL6 小鼠，以观察硝化 Trx-1（N-Trx-1）对肺纤维化的影响。在 C57/BL6 小鼠博莱霉素诱导的肺纤维化模型中，我们发现随着肺泡上皮细胞（AECs）凋亡的增加，硝化 Trx 增加，而其活性降低，这与 p38-MAPK 途径有关。我们的研究结果表明，AG 或 rhTrx-1 而非 N-Trx-1 可显著减轻肺纤维化。综上所述，这些结果表明，阻断 Trx-1 硝化或补充外源性 rhTrx-1，可能为特发性肺纤维化患者的肺纤维化治疗提供新的策略。
