Fu San, Tang Xiaoyan, Xu Yiming, Song Xianrui, Qian Xiuhui, Hu Yingying, Zhang Mian
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Life (Basel). 2022 Nov 23;12(12):1961. doi: 10.3390/life12121961.
Idiopathic pulmonary fibrosis (IPF) is an age-related interstitial lung disease with a high incidence in the elderly. Although many reports have shown that senescence can initiate pulmonary fibrosis, the relationship between aging and pulmonary fibrosis has not been explained systematically. In our study, young and old rats were intratracheally instilled with bleomycin (1 mg/kg), and the basic pathological indexes were determined using a commercial kit, hematoxylin, and eosin (H&E) and Masson's Trichrome staining, immunohistochemistry, immunohistofluorescence, and q-PCR. Then, the lung tissues of rats were sequenced by next-generation sequencing for transcriptome analysis. Bioinformatics was performed to analyze the possible differences in the mechanism of pulmonary fibrosis between aged and young rats. Finally, the related cytokines were determined by q-PCR and ELISA. The results indicate that pulmonary fibrosis in old rats is more serious than that in young rats under the same conditions. Additionally, transcriptomic and bioinformatics analysis with experimental validation indicate that the differences in pulmonary fibrosis between old and young rats are mainly related to the differential expression of cytokines, extracellular matrix (ECM), and other important signaling pathways. In conclusion, aging mainly affects pulmonary fibrosis through the ECM-receptor interaction, immune response, and chemokines.
特发性肺纤维化（IPF）是一种与年龄相关的间质性肺疾病，在老年人中发病率较高。尽管许多报告表明衰老可引发肺纤维化，但衰老与肺纤维化之间的关系尚未得到系统解释。在我们的研究中，对年轻和老年大鼠气管内注入博来霉素（1 mg/kg），并使用商业试剂盒、苏木精和伊红（H&E）染色、Masson三色染色、免疫组织化学、免疫荧光和q-PCR测定基本病理指标。然后，对大鼠肺组织进行二代测序以进行转录组分析。运用生物信息学分析老年和年轻大鼠肺纤维化机制的可能差异。最后，通过q-PCR和ELISA测定相关细胞因子。结果表明，在相同条件下，老年大鼠的肺纤维化比年轻大鼠更严重。此外，转录组学和生物信息学分析以及实验验证表明，老年和年轻大鼠肺纤维化的差异主要与细胞因子、细胞外基质（ECM）和其他重要信号通路的差异表达有关。总之，衰老主要通过ECM-受体相互作用、免疫反应和趋化因子影响肺纤维化。
