Laboratório de Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul-PUCRS, Porto Alegre, Brazil.
Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul-PUCRS, Porto Alegre, Brazil.
Inflammation. 2018 Oct;41(5):1987-2001. doi: 10.1007/s10753-018-0842-3.
Pulmonary fibrosis is a specific form of interstitial pneumonia. In addition to the idiopathic cause, it may be caused by drugs such as bleomycin (BLM)-used in the treatment of tumors. Fructose-1,6-bisphosphate (FBP) is a high-energy endogenous glycolytic compound that has antifibrotic, anti-inflammatory, and immunomodulatory effects. The aim of this study was to investigate the effects of FBP on both BLM-induced pulmonary fibrosis in mice and in a human embryonic lung fibroblast (MRC-5) culture system. C57BL/6 mice were divided into four groups: control, FBP, BLM, and BLM plus FBP. A single dose of bleomycin (7.5 U/kg) was administered intratracheally, and survival, body weight, Ashcroft score, and histological analysis were evaluated. Pulmonary function and bronchoalveolar lavage fluid (BALF) were also evaluated after a single dose of bleomycin (1.2 U/kg-intratracheally). Treatment with FBP (500 mg/kg) was given on day 0 intraperitoneally. Fibroblasts (MRC-5 cells) were used to access the effect of FBP in vitro. In vivo, FBP increased the survival rate and reduced body weight loss (BLM vs. BLM plus FBP-p < 0.05). FBP also prevented BLM-induced loss of pulmonary function and decreased BALF inflammatory cells, level of fibrosis, and superficial collagen density (p < 0.05). In vitro, FBP (0.62 and 1.25 mM) had inhibitory activity on MRC-5 cells and was able to induce senescence in fibroblasts. These results showed that FBP has the potential of reducing the toxic effects of BLM and may provide supportive therapy for conventional methods used for the treatment of cancer.
肺纤维化是一种特发性间质性肺炎。除特发性原因外，还可能由博莱霉素（BLM）等药物引起，用于治疗肿瘤。1,6-二磷酸果糖（FBP）是一种高能内源性糖酵解化合物，具有抗纤维化、抗炎和免疫调节作用。本研究旨在探讨 FBP 对博莱霉素诱导的小鼠肺纤维化和人胚肺成纤维细胞（MRC-5）培养系统的影响。C57BL/6 小鼠分为四组：对照组、FBP 组、BLM 组和 BLM+FBP 组。气管内单次给予博莱霉素（7.5 U/kg），评价生存情况、体重、Ashcroft 评分和组织学分析。单次气管内给予博莱霉素（1.2 U/kg）后，还评价了肺功能和支气管肺泡灌洗液（BALF）。FBP（500 mg/kg）于第 0 天腹腔内给药。使用成纤维细胞（MRC-5 细胞）来评估 FBP 在体外的作用。在体内，FBP 提高了存活率并减少了体重减轻（BLM 与 BLM+FBP 相比，p<0.05）。FBP 还防止了 BLM 诱导的肺功能丧失，并降低了 BALF 中的炎症细胞、纤维化程度和表面胶原密度（p<0.05）。在体外，FBP（0.62 和 1.25 mM）对 MRC-5 细胞具有抑制活性，并能诱导成纤维细胞衰老。这些结果表明，FBP 具有减轻 BLM 毒性作用的潜力，可为癌症的常规治疗方法提供支持性治疗。
