Department of Animal Science, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, P. R. China.
Department of Biochemistry and Molecular Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, P. R. China.
Mol Nutr Food Res. 2022 Feb;66(3):e2100952. doi: 10.1002/mnfr.202100952. Epub 2021 Dec 21.
Acute lung injury (ALI) is characterized by severe inflammation. Vitamin D3 is discussed to reduce inflammation in ALI, but the mechanism is not well understood. This study assesses the effect of different calcitriol administration strategies on inflammation and the lung microbiota composition in ALI. In a mouse model, the alveolus and airway pathology are assessed by immunohistology. mRNA expression is determined by Real-Time Quantitative PCR and protein expressions is detected by Western-blotting. The composition of microbiota is performed by 16s DNA high-throughput sequencing. Short-term vitamin D3 supplementation prevents lipopolysaccharide-induced ALI by preventing pro-inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). In contrast, long-term treatment over 3 days, 6 days, or 10 days had no such effect. Short-term vitamin D3, but not long-term pretreatment significantly reduces the phosphorylation of signal transducer and activator of transcription 3 and suppressor of cytokine signaling 3, but upregulates the phosphorylation of inhibitor of nuclear factor-κ-gene binding. Furthermore, an increased relative abundance of Rodentibacter genus in LPS-challenged mice bronchoalveolar lavage fluid is observed, which is sensitive to short-term vitamin D3 treatment, effectively alleviating the Rodentibacter abundance. Correlation analysis shows that the load of Rodentibacter positively correlated with the IL-1β, IL-6, and TNF-α gene expression. The data support that a single administration of vitamin D3 may work as an adjuvant therapy for acute lung inflammation.
急性肺损伤（ALI）的特征是严重的炎症。维生素 D3 被认为可以减轻 ALI 的炎症，但机制尚不清楚。本研究评估了不同的骨化三醇给药策略对 ALI 中炎症和肺微生物群组成的影响。在小鼠模型中，通过免疫组织化学评估肺泡和气道病理。通过实时定量 PCR 确定 mRNA 表达，通过 Western-blotting 检测蛋白表达。通过 16s DNA 高通量测序检测微生物群的组成。短期维生素 D3 补充通过预防包括白细胞介素 1β（IL-1β）、白细胞介素 6（IL-6）和肿瘤坏死因子 α（TNF-α）在内的促炎细胞因子，预防脂多糖诱导的 ALI。相比之下，3 天、6 天或 10 天的长期治疗则没有这种效果。短期维生素 D3，但不是长期预处理，显著降低信号转导和转录激活因子 3 和细胞因子信号转导抑制因子 3 的磷酸化，但上调核因子-κB 基因结合抑制物的磷酸化。此外，在 LPS 挑战的小鼠支气管肺泡灌洗液中观察到 Rodentibacter 属的相对丰度增加，这对短期维生素 D3 治疗敏感，有效缓解了 Rodentibacter 的丰度。相关性分析表明，Rodentibacter 的负荷与 IL-1β、IL-6 和 TNF-α基因表达呈正相关。数据支持单次给予维生素 D3 可能作为急性肺炎症的辅助治疗。
