| 徐芳蓉,刘轶宁,杨翠翠,王 晶,陆劲红,苗登顺.活性维生素D缺乏诱发与衰老相关的特发性肺纤维化[J].,2022,(17):3208-3213 |
| 活性维生素D缺乏诱发与衰老相关的特发性肺纤维化 |
| Active Vitamin D Deficiency Induces Aging-related Idiopathic Pulmonary Fibrosis |
| 投稿时间：2022-02-25 修订日期：2022-03-21 |
| DOI：10.13241/j.cnki.pmb.2022.17.002 |
| 中文关键词: 衰老 活性维生素D 肺纤维化 |
| 英文关键词: Aging Vitamin D Pulmonary Fibrosis |
| 基金项目:国家自然科学基金重点项目（81730066）；江苏省研究生创新计划项目（KYCX20_1381） |
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| 中文摘要: |
| 摘要 目的：研究活性维生素D缺乏致小鼠肺纤维化的作用与机制。方法：取7周龄同窝野生型（Wild Type, WT）小鼠，维生素D缺乏（1α(OH)ase-/-）小鼠置于肺功能检测仪器中，对其吸气时间，最大吸气流速、呼出50%气量时对应的呼气流速、潮气量、分钟通气量，呼吸频率等指标进行分析。培养小鼠原代肺成纤维细胞，按基因型分为对照组、活性维生素D缺乏组，之后分组检测细胞SA-β-gal阳性率。另外取小鼠肺组织样本多聚甲醛固定后脱水浸蜡以制作石蜡组织切片， 对各组切片进行HE、Masson染色以观察肺的组织学形态的变化，使用免疫组织化学观察肺组织中的衰老相关蛋白（p16、p53）的表达量差异。结果：相较于同窝WT小鼠，1α(OH)ase-/-小鼠通气功能显著减弱，肺成纤维细胞衰老程度和肺组织纤维化程度均有不同程度增加，且免疫组化结果显示肺组织中与衰老相关的p53及p16阳性的细胞也显著增加。结论：活性维生素D的缺乏能够诱发与衰老相关的特发性肺纤维化，可能的机制是通过激活p53/p16信号引发肺成纤维细胞提前衰老，继而引起肺组织异常纤维化。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect and mechanism of vitamin D deficiency on pulmonary fibrosis in mice. Methods: The 7-week-old of wild type (WT) mice and vitaminD deficiency（1α(OH)ase-/-） mice were used in this study. They were mechanically ventilated at an initial baseline challenge using the pulmonary function testing instrument（WBP-8MR, TOW-INT TECH, Shanghai, China） to directly evaluate lung ventilatory resistance and compliance, including inspiration time, peak inspiratory flow, expiration time, frequency, tidal volume, minute volume. The lungs were separated, minced, and digested to culture pulmonary fibroblasts, and then analyzing the percentages of SA-β-gal-positive cells or areas. The pathological changes of lung tissues and the distribution collagen fibers were observed by HE and Masson staining. The expression of p53, p16 of lung tissues were detected by immunohistochemistry staining. Results: Compared with WT littermates, the ventilation function of 1α(OH)ase-/- mice was significantly weakened, and the degree of senescence of lung fibroblasts and the degree of lung tissue fibrosis were increased to varying degrees, and immunohistochemical results showed that the number of p53 and p16 positive cells associated with senescence also increased significantly. Conclusion: Lack of vitamin D can promote pulmonary fibrosis, and the possible mechanism is that the activation of p53/p16 signaling pathway induces premature senescence of lung fibroblasts, which in turn causes abnormal fibrosis of lung tissue. |
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