关键词: Idiopathic pulmonary fibrosis Intermittent fasting Monocyte Monocyte-derived alveolar macrophage Treg

来  源:   DOI:10.1016/j.advms.2024.07.004

Abstract:
OBJECTIVE: Idiopathic pulmonary fibrosis (IPF), a chronic and progressively worsening condition characterized by interstitial lung inflammation and fibrosis of unknown etiology, has a grim prognosis. The treatment options for IPF are limited and new therapeutic strategies are urgently needed. Dietary restriction can improve various inflammatory diseases, but its therapeutic effect on bleomycin (BLM)-induced pulmonary fibrosis mouse model remains unclear. This study aims to investigate whether intermittent fasting (IF) can alleviate BLM-induced pulmonary inflammation and fibrosis.
METHODS: Pulmonary fibrosis mouse models were induced by BLM. The IF group underwent 24-h fasting cycles for one week prior and three weeks following BLM administration. Meanwhile, the ad libitum feeding group had unrestricted access to food throughout the experiment. The evaluation focused on lung pathology via histological staining, qPCR analysis of collagen markers, and immune cell profiling through flow cytometry.
RESULTS: IF group significantly reduced inflammation and fibrosis in lung tissues of BLM-induced mice compared to ad libitum feeding group. qPCR results showed IF remarkably decreased the mRNA expression of Col 1a and Col 3a in the lungs of BLM-induced mouse models. IF also reduced the numbers of regulatory T cells (Tregs), T helper 17 (Th17) cells, monocytes, and monocyte-derived alveolar macrophages (MoAMs) in the lung tissues.
CONCLUSIONS: IF may improve BLM-induced pulmonary fibrosis by decreasing numbers of immune cells including Treg cells, Th17 ​cells, monocytes, and MoAMs in the lungs. This study offers experimental validation for dietary intervention as a viable treatment modality in IPF management.
摘要:
目的:特发性肺纤维化(IPF),以间质性肺部炎症和病因不明的纤维化为特征的慢性和逐渐恶化的病症,有一个严峻的预后。IPF的治疗选择有限,迫切需要新的治疗策略。限制饮食可以改善各种炎症性疾病,但其对博来霉素(BLM)诱导的肺纤维化小鼠模型的治疗效果尚不清楚。本研究旨在探讨间歇性禁食(IF)是否可以减轻BLM诱导的肺部炎症和纤维化。
方法:BLM诱导肺纤维化小鼠模型。IF组在BLM给药前一周和给药后三周进行24小时禁食周期。同时,在整个实验过程中,随意喂养组可以不受限制地获取食物。通过组织学染色对肺病理学进行评估,胶原蛋白标记的qPCR分析,和通过流式细胞术进行免疫细胞谱分析。
结果:与随意喂养组相比,IF组显著降低了BLM诱导小鼠肺组织的炎症和纤维化。qPCR结果显示,IF可显著降低BLM诱导小鼠肺组织中Col1a和Col3a的mRNA表达。如果还减少了调节性T细胞(Tregs)的数量,辅助性T细胞17(Th17),单核细胞,和肺组织中单核细胞来源的肺泡巨噬细胞(MoAMs)。
结论:IF可能通过减少包括Treg细胞在内的免疫细胞数量来改善BLM诱导的肺纤维化,Th17细胞,单核细胞,和肺部的MoAM。这项研究为饮食干预作为IPF管理中可行的治疗方式提供了实验验证。
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