Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Am J Obstet Gynecol. 2012 Jul;207(1):76.e25-32. doi: 10.1016/j.ajog.2012.04.025. Epub 2012 Apr 30.
We sought to investigate the effects of antenatal retinoic acid on the pulmonary vasculature and vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) expression in a nitrofen-induced congenital diaphragmatic hernia (CDH) model.
Rat fetuses were exposed to nitrofen at gestational day 9.5 and/or all-trans retinoic acid (ATRA) at gestational days 18.5-20.5. We assessed lung growth, airway, and vascular morphometry. VEGF, VEGFR1, and VEGFR2 expression was analyzed by Western blotting and immunohistochemistry. Continuous data were analyzed by analysis of variance and Kruskal-Wallis test.
CDH decreased lung to body weight ratio, increased mean linear intercept and mean transection length/airspace, and decreased mean airspace cord length. ATRA did not affect lung growth or morphometry. CDH increased proportional medial wall thickness of arterioles while ATRA reduced it. ATRA recovered expression of VEGF and receptors, which were reduced in CDH.
Retinoic acid and VEGF may provide pathways for preventing pulmonary hypertension in CDH.
我们旨在研究产前维甲酸对硝基呋喃诱导的先天性膈疝（CDH）模型肺血管和血管内皮生长因子（VEGF）及其受体（VEGFR）表达的影响。
大鼠胎儿于妊娠第 9.5 天接触硝基呋喃，或于妊娠第 18.5-20.5 天接触全反式维甲酸（ATRA）。我们评估了肺生长、气道和血管形态计量学。通过 Western blot 和免疫组织化学分析 VEGF、VEGFR1 和 VEGFR2 的表达。连续数据采用方差分析和 Kruskal-Wallis 检验进行分析。
CDH 降低了肺与体重的比值，增加了平均线性截距和平均横截面积/气腔，以及降低了平均气腔索长。ATRA 不影响肺生长或形态计量学。CDH 增加了小动脉中膜壁厚度的比例，而 ATRA 则降低了它。ATRA 恢复了在 CDH 中降低的 VEGF 和受体的表达。
维甲酸和 VEGF 可能为预防 CDH 中的肺动脉高压提供途径。
