Department of Pediatrics, Langdong Hospital of Guangxi Medical University, No 60 Jinhu Road, Qingxiu district, Nanning city, Guangxi Zhuang Autonomous Region, China.
Department of Pediatrics, Langdong Hospital of Guangxi Medical University, No 60 Jinhu Road, Qingxiu district, Nanning city, Guangxi Zhuang Autonomous Region, China.
Biomed Pharmacother. 2021 Sep;141:111836. doi: 10.1016/j.biopha.2021.111836. Epub 2021 Jun 29.
To investigate the therapeutic effects of vitamin A (VitA) or vitamin D (VitD) against bronchopulmonary dysplasia (BPD) and the underlying mechanism from the perspective of macrophage polarization.
A BPD model was established on rats. Hematoxylin and eosin staining was used to evaluate the pathological state of lung tissues. The expression of CD68 was determined by immunohistochemistry assay. The infiltration of M1 and M2 macrophages was marked by immunofluorescence. The expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-10, nitric oxide synthase (NOS), and arginase-1 (Arg-1) were evaluated by quantitative reverse transcription polymerase chain reaction assay, and the ratio of M1/M2 in the bronchoalveolar lavage fluid was determined by flow cytometry.
Disordered alveolar structure in the lung tissue, thickened alveolar septa, and infiltration of inflammatory cells around the alveolar cavity and pulmonary septa were observed in lipopolysaccharide (LPS)-treated rats. On day 21 post-natal (PN21), the pathological state was aggravated, alveolar simplification was observed, and the expression level of CD68 in the lung tissues was significantly elevated, and these results were dramatically alleviated in the VitA, VitD, and VitA+VitD groups. However, no significant synergistic effect was observed between VitA+VitD and VitA or VitD groups. After the administration with VitA or VitD, IL-10 and Arg-1 were up-regulated on PN10. TNF-α and NOS were up-regulated on PN21. The ratio of macrophage polarization and M2 macrophages increased considerably after the stimulation with LPS, and this result was significantly reversed by VitA or VitD. A significant difference was observed on the effect of different dosages of VitA or VitD on macrophage polarization, among which moderate dosages of VitA or VitD exerted the most significant influence on macrophage polarization.
The BPD-linked pulmonary injury stimulated by LPS can be ameliorated by the introduction of VitA or VitD.
从巨噬细胞极化的角度探讨维生素 A（VitA）或维生素 D（VitD）治疗支气管肺发育不良（BPD）的疗效及其潜在机制。
建立大鼠 BPD 模型。采用苏木精-伊红染色评估肺组织的病理状态。免疫组织化学法检测 CD68 的表达。免疫荧光法标记 M1 和 M2 巨噬细胞浸润。采用定量逆转录聚合酶链反应法检测肿瘤坏死因子（TNF）-α、白细胞介素（IL）-10、一氧化氮合酶（NOS）和精氨酸酶-1（Arg-1）的表达水平，通过流式细胞术测定支气管肺泡灌洗液中 M1/M2 的比值。
脂多糖（LPS）处理的大鼠肺组织可见肺泡结构紊乱，肺泡隔增厚，肺泡腔和肺间隔周围炎性细胞浸润。PN21 时，病理状态加重，肺泡结构简化，肺组织 CD68 表达水平显著升高，VitA、VitD 和 VitA+VitD 组明显缓解。然而，VitA+VitD 与 VitA 或 VitD 组之间未见明显协同作用。给予 VitA 或 VitD 后，PN10 时 IL-10 和 Arg-1 上调，PN21 时 TNF-α 和 NOS 上调。LPS 刺激后，巨噬细胞极化和 M2 巨噬细胞的比例显著增加，VitA 或 VitD 显著逆转了这一结果。VitA 或 VitD 对巨噬细胞极化的不同剂量作用存在显著差异，其中 VitA 或 VitD 的中剂量对巨噬细胞极化的影响最为显著。
LPS 刺激引起的 BPD 相关肺损伤可通过引入 VitA 或 VitD 得到改善。
