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评价成纤维细胞生长因子 21 在博莱霉素诱导的肺纤维化中的防治效果。

Evaluation of prevention and treatment effects of fibroblast growth factor-21 in BLM-induced pulmonary fibrosis.

机构信息

Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China.

Institute of Microbiology, Heilongjiang Academy of Sciences, Harbin, 150010, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2023 Nov;396(11):3299-3313. doi: 10.1007/s00210-023-02540-3. Epub 2023 May 31.

DOI:10.1007/s00210-023-02540-3
PMID:37256335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10230495/
Abstract

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease and associated with a high mortality rate. In the study, the prevention and treatment effects of fibroblast growth factor-21 (FGF-21) in bleomycin (BLM)-induced pulmonary fibrosis were investigated in vivo and vitro. In the prevention of pulmonary fibrosis studies, the results showed that interdict of FGF-21 could reduce the related gene and protein expression levels of pulmonary fibrosis. In addition, FGF-21 significantly reduced both the aggregation of inflammatory cells and deposition of collagen in the lung by histopathology. In therapy of pulmonary fibrosis studies, the results indicated that treatment with FGF-21 resulted in an amelioration of the pulmonary fibrosis in mice with reductions of the pathological score, collagen deposition and transforming growth factor (TGF)-β and α-smooth muscle actin (α-SMA) expressions in the lung tissues at fibrotic stage, and late administration was also able to reduce the degree of pulmonary fibrosis and even better than these in the prevention group. Furthermore, BLM-induced THP-1 macrophage model was verified using FGF-21; the result showed that FGF-21 decreased the related gene expression level of pulmonary fibrosis. FGF-21 may have preventive and therapeutic effects on BLM-induced pulmonary fibrosis via inhibiting myofibroblast differentiation and inflammatory. Thus, FGF-21 represents a potential drug for the prevention and treatment of pulmonary fibrosis.

摘要

肺纤维化是一种进行性和致命性的肺纤维化疾病,与高死亡率相关。在这项研究中,研究人员在体内和体外研究了成纤维细胞生长因子-21(FGF-21)在博来霉素(BLM)诱导的肺纤维化中的预防和治疗作用。在预防肺纤维化的研究中,结果表明,抑制 FGF-21 可以降低肺纤维化的相关基因和蛋白表达水平。此外,FGF-21 通过组织病理学明显减少了炎症细胞的聚集和胶原在肺中的沉积。在肺纤维化治疗的研究中,结果表明,FGF-21 治疗可改善肺纤维化小鼠的肺纤维化,降低病理评分、胶原沉积和转化生长因子(TGF)-β和α-平滑肌肌动蛋白(α-SMA)在纤维化阶段肺组织中的表达,晚期给药也能减轻肺纤维化程度,甚至优于预防组。此外,还使用 FGF-21 验证了 BLM 诱导的 THP-1 巨噬细胞模型;结果表明,FGF-21 降低了肺纤维化的相关基因表达水平。FGF-21 可能通过抑制肌成纤维细胞分化和炎症对 BLM 诱导的肺纤维化具有预防和治疗作用。因此,FGF-21 是预防和治疗肺纤维化的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/10230495/c9cce7178a8d/210_2023_2540_Fig5a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/10230495/76d895803a06/210_2023_2540_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/10230495/e16e332f49c7/210_2023_2540_Fig2a_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/10230495/bc6f1007a9e8/210_2023_2540_Fig4a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/10230495/c9cce7178a8d/210_2023_2540_Fig5a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/10230495/76d895803a06/210_2023_2540_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/10230495/e16e332f49c7/210_2023_2540_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/10230495/95553bd7b1f1/210_2023_2540_Fig3a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/10230495/bc6f1007a9e8/210_2023_2540_Fig4a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4a/10230495/c9cce7178a8d/210_2023_2540_Fig5a_HTML.jpg

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