Vitamin D: Feel It in More Than Just Your Bones!
Vitamin D: Feel It in More Than Just Your Bones!
复制标题
维生素 D：不仅仅是在骨骼中感受到它！
DOI：
10.1165/rcmb.2020-0072ed
复制
发表时间：
2020
影响因子：
6.4
通讯作者：
Cornfield,DavidN
中科院分区：
文献类型：
--
作者：
Cornfield,DavidN
1967年，Northway及其同事在《新英格兰医学杂志》上发表了一篇具有里程碑意义的文章，描述了新生儿肺透明膜病呼吸机治疗后的肺部疾病（1）。他们指出，这种新的疾病与机械通气和“高氧超过150小时（6天）”有关（1）。尽管在过去的50年里护理有了巨大的改善，但这种名为支气管肺发育不良（BPD）的疾病仍然存在，发病率实际上正在增加（2）。在本期杂志中，Mandell和他的同事们（pp. 79-91）报道了BPD的新原因和推定的治疗方法（3）。作者认为，令人信服的是，维生素D在肺发育中起着重要作用，维生素D缺乏症（VDD）可能会增加新生儿肺对高氧暴露损伤的易感性（3）。从根本上说，这些结果为维生素D在肺中引起基因组反应的命题提供了支持。作者提供的证据表明，这种作用可能是由HIF-1a（缺氧诱导因子-1a）及其下游靶点VEGF（血管内皮生长因子）介导的（4）。鉴于BPD或婴儿期慢性肺部疾病的发病率逐渐增加，特别是在极低出生体重儿中，这些发现的意义是显著的（5）。结论基于明确的数据，表明母体VDD损害新生儿肺远端结构和肺功能，包括气道反应性增加。有趣的是，肺在肺发育的肺泡阶段得到了很好的评价，这表明VDD对结构和功能的持久和长期影响。这些数据是第一次证明远端空域和血管疾病与母体VDD。临床研究表明，患有VDD的母亲的孩子患哮喘和喘息的风险增加，进一步放大了研究结果的意义（6）。考虑到来自同一组研究人员的先前报告，表明产前维生素D治疗可以保护BPD实验模型中的肺生长并预防肺动脉高压（7），目前的数据强调了维生素D在预防新生儿肺部疾病方面的潜在治疗作用。研究人员通过询问可能构成维生素D作用基础的分子途径扩展了他们的发现。具体来说，正如作者所指出的，在具有母体VDD的动物中血管密度减少，测量了全肺HIF-1a和VEGF基因和蛋白。母体VDD降低全肺VEGF，但不降低HIF-a基因表达。高氧暴露降低HIF-1a、维生素D受体和VEGF受体2的表达。总之，这些结果表明维生素D在调节远端新生儿肺结构和功能中具有明确的作用（3）。
In 1967, Northway and colleagues published a landmark piece describing pulmonary disease in newborns after respirator therapy for hyaline membrane disease in the New England Journal of Medicine (1). They noted that the new disease was associated with mechanical ventilation and “high oxygen for longer than 150 hours (6 d)”(1). Notwithstanding immense improvements in care over the past 5 decades, the disease, named bronchopulmonary dysplasia (BPD), persists, with an incidence that is actually increasing (2). In this issue of the Journal, Mandell and colleagues (pp. 79–91) report on a novel cause and putative therapeutic approach to BPD (3). The authors argue, compellingly, that vitamin D plays a significant role in lung development and that vitamin D deficiency (VDD) may increase the susceptibility of the neonatal lung to injury due to hyperoxia exposure (3). Fundamentally, these results offer support for the proposition that vitamin D elicits a genomic response in the lung. The authors provide evidence that the effects may be mediated by HIF-1a (hypoxia-inducible factor-1a) and its downstream target, VEGF (vascular endothelial growth factor)(4). Given the progressively increasing incidence of BPD, or chronic lung disease of infancy, especially in very-low-birthweight infants, the implications of these findings are significant (5).The conclusions are based on clear data demonstrating that maternal VDD compromises both neonatal lung distal structure and pulmonary function, including increased airway reactivity. Interestingly, the lungs were evaluated well into the alveolar stage of lung development, suggesting durable and long-lived effects of VDD on both structure and function. These data are the first to demonstrate distal airspace and vascular disease in association with maternal VDD. Clinical studies demonstrating that children of mothers with VDD are at increased risk of asthma and wheezing further amplify the significance of the findings (6). Considered in concert with prior reports from the same group of investigators demonstrating that antenatal vitamin D therapy preserves lung growth and prevents pulmonary hypertension in an experimental model of BPD (7), the present data underscore a potential therapeutic role for vitamin D in preventing neonatal lung disease. The investigators extended their findings by interrogating the molecular pathways that might underlie the vitamin D effects. Specifically, as the authors noted diminished vascular density in the animals with maternal VDD, whole-lung HIF-1a and VEGF gene and protein were measured. Maternal VDD decreased whole-lung VEGF, but not HIF-a gene expression. Hyperoxia exposure decreased expression of HIF-1a, vitamin D receptor, and VEGF receptor 2. Taken together, these results point to a clear role for vitamin D in modulating distal neonatal lung structure and function (3).