维生素 D 缺乏对子代大鼠肺形态结构及血小板源性生长因子-A 表达的影响

Effect of maternal vitamin D deficiency on lung morphogenesis and platelet-derived growth factor-A expression in rat offspring

摘要:

目的：研究孕期维生素 D（VitD）缺乏对子代大鼠肺形态发育及血小板源性生长因子-A（PDGF-A）表达的影响。方法：雌性Sprague-Dawley (SD) 大鼠随机分为对照组、VitD 缺乏模型组（每组6只）。对照组正常饲养；模型组予以避光、不含 VitD 的饲料喂养，2周后与成熟 SD 雄性大鼠交配，每组取孕20 d的胎肺及生后1 d 新生鼠肺，光镜及电镜下观察肺形态结构， RT-PCR 及 Western blot 分别检测肺组织PDGF-A mRNA及蛋白水平的表达。结果：光镜下，模型组子鼠肺泡平均表面积、平均呼吸膜周径均小于对照组（P<0.05），平均肺泡间隔厚度大于对照组（P<0.05）；电镜下，模型组子鼠的板层小体数量明显少于对照组，成熟细胞器较少见。RT-PCR 及 Western blot结果显示模型组子鼠肺组织PDGF-A mRNA和蛋白表达水平均低于对照组（P<0.05）。结论：孕期 VitD 缺乏抑制孕晚期胎鼠及新生大鼠的肺形态发育。VitD 缺乏能显著抑制肺组织 PDGF-A 表达；PDGF-A表达减低可能是VitD缺乏抑制大鼠肺发育的重要机制之一。

Abstract:

OBJECTIVE: To study the effect of maternal vitamin D deficiency on lung morphogenesis and platelet-derived growth factor-A (PDGF-A) expression in rat offspring. METHODS: Sprague-Dawley (SD) female rats were randomly divided into two groups: normal control and vitamin D deficiency, with 6 rats in each group. The vitamin D deficiecy group was kept away from light and fed with the forage without vitamin D. After 2 weeks, the rats were mated with normal SD male rats. The morphological changes of fetal rat lungs on day 20 of gestation and 1-day-old neonatal rat lungs were observed by light microscope and electronic microscope. The levels of PDGF-A mRNA and protein in fetal and neonatal rat lungs were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) technique and Western blot method respectively. RESULTS: Under the light microscope, smaller alveolar space, smaller diameter of the respiratory membrane and thicker alveolus mesenchyma were observed in lungs of fetal and neonatal rats from the vitamin D deficiency group compared with the controls (P<0.05). Under the electronic microscope, fewer lamellar bodies but more glycogen deposition in intracytoplasm were observed in the lungs of fetal rats from the vitamin D deficiency group compared with the controls. There was an increased number of empty lamellar bodies in neonatal rats from the vitamin D deficiency group. The levels of PDGF-A mRNA and protein in lungs of fetal and neonatal rats from the vitamin D deficiency group were significantly lower than the controls (P<0.05). CONCLUSIONS: Maternal vitamin D deficiency during pregnancy may inhibit the development of lung morphogenesis and PDGF-A expression in late fetal and neonatal rats. The low expression of PDGF-A may be involved in the inhibitory effect of vitamin D deficiency on the lung development.