Lykkedegn Sine, Sorensen Grith Lykke, Beck-Nielsen Signe Sparre, Pilecki Bartosz, Duelund Lars, Marcussen Niels, Christesen Henrik Thybo
Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Clinical Institute, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
PLoS One. 2016 Aug 29;11(8):e0155203. doi: 10.1371/journal.pone.0155203. eCollection 2016.
Animal studies suggest a role of vitamin D in fetal lung development although not studied in preterm animals. We tested the hypothesis that vitamin D depletion aggravates respiratory insufficiency in preterm rat offspring. Furthermore, the effects of vitamin D depletion on growth and lung surfactant were investigated. Female Sprague-Dawley rats were randomly assigned low vitamin D (VDL) or control diet before mating and followed with serum 25-hydroxyvitamin D (s-25(OH)D) determinations. After cesarean section at gestational day 19 (E19) or day 22 (E22), placental weight, birth weight, crown-rump-length (CRL), oxygenation (SaO2) at 30 min and survival time were recorded. The pup lungs were analyzed for phospholipid levels, surfactant protein A-D mRNA and the expression of the vitamin D receptor (VDR). S-25(OH)D was significantly lower in the VDL group at cesarean section (12 vs. 30nmol/L, p<0.0001). Compared to the controls, E19 VDL pups had lower birth weight (2.13 vs. 2.29g, p<0.001), lung weight (0.09 vs. 0.10g, p = 0.002), SaO2 (54% vs. 69%, p = 0.002) as well as reduced survival time (0.50 vs. 1.25h, p<0.0001). At E22, the VDL-induced pulmonary differences were leveled out, but VDL pups had lower CRL (4.0 vs. 4.5cm, p<0.0001). The phospholipid levels and the surfactant protein mRNA expression did not differ between the dietary groups. In conclusion, Vitamin D depletion led to lower oxygenation and reduced survival time in the preterm offspring, associated with reduced lung weight and birth weight. Further studies of vitamin D depletion in respiratory insufficiency in preterm neonates are warranted.
动物研究表明维生素D在胎儿肺发育中发挥作用,尽管尚未在早产动物中进行研究。我们检验了以下假设:维生素D缺乏会加重早产大鼠后代的呼吸功能不全。此外,还研究了维生素D缺乏对生长和肺表面活性物质的影响。在交配前,将雌性斯普拉格-道利大鼠随机分为低维生素D(VDL)组或对照组饮食,并随后测定血清25-羟基维生素D(s-25(OH)D)。在妊娠第19天(E19)或第22天(E22)剖宫产术后,记录胎盘重量、出生体重、顶臀长度(CRL)、30分钟时的氧合情况(SaO2)和存活时间。对幼鼠肺进行磷脂水平、表面活性物质蛋白A-D mRNA以及维生素D受体(VDR)表达的分析。剖宫产时,VDL组的s-25(OH)D显著降低(12对30nmol/L,p<0.0001)。与对照组相比,E19的VDL幼鼠出生体重较低(2.13对2.29g,p<0.001)、肺重量较低(0.09对0.10g,p = 0.002)、SaO2较低(54%对69%,p = 0.002),且存活时间缩短(0.50对1.25小时,p<0.0001)。在E22时,VDL诱导的肺部差异趋于平稳,但VDL幼鼠的CRL较低(4.0对4.5cm,p<0.0001)。饮食组之间的磷脂水平和表面活性物质蛋白mRNA表达没有差异。总之,维生素D缺乏导致早产后代的氧合降低和存活时间缩短,与肺重量和出生体重降低有关。有必要进一步研究早产新生儿呼吸功能不全中维生素D缺乏的情况。