维生素E对先天性膈疝大鼠模型胎仔肺发育及肺血管重构的影响

Effect of vitamin E on lung development and vascular remodeling in fetal rats with congenital diaphragmatic hernia

目的探讨维生素E对先天性膈疝(CDH)大鼠模型胎仔肺发育不良和肺血管重构的影响。方法将18只SD雌鼠定时配种成功后分为对照组、膈疝组和干预组,以除草醚诱导建立大鼠CDH动物模型,并以维生素E进行干预,第21 d剖宫取出胎鼠及其肺组织,进行光镜及电镜观察,结果进行图像及统计学分析。结果干预组膈疝致畸率46.34%小于膈疝组致畸率66.67%(P<0.05)。干预组胎肺发育接近对照组,其肺重/体重值[(3.45±0.58)mg/g]、轴向腺泡计数(4.4±0.3)、肺泡面积比例[(63.7±5.6)%]和肺泡面积比[(45±6)%]均大于膈疝组[(2.36±0.61)mg/g、(2.3±0.2)%、[(46.5±7.3)%]、[(27±6.7)%],P<0.01],而肺泡间隔面积比[(45±6.8)%]低于膈疝组[(63±8.3)%,P<0.01];同时腺泡前内动脉(PAPA/IAPA)的平均中膜厚度百分比[(22.1±2.2)%、(17.6±2.8)%]低于膈疝组[(24.3±4.0)%、(21.5±2.9)%,P<0.01];单位视野内腺泡内动脉(IAPA)非肌型血管的比例[(79.4±3.2)%]高于膈疝组[(71.6±3.3)%,P<0.01],小动脉的肌化受到抑制。结论维生素E产前干预能降低CDH大鼠模型胎仔膈疝的发生率,并且有助于促进CDH胎仔肺的发育,抑制其肺血管重构。

Objective To discuss the effect of vitamin E on lung development and vascular remodeling in fetal rats with congenital diaphragmatic hernia （CDH）. Methods Eighteen pregnant SD rats were randomly divided into 3 groups： control group, CDH group and intervention group. Rats in CDH group and intervention group underwent intragastric administration with nitrofen 125 mg （soluble in olive oil 2 ml）. Rats in control group were given olive oil 2 ml. Rats in intervention group were given vitamin E 140 mg/kg （ soluble in alcohol 2 ml） q. d for 3 days from the 11 th day of pregnancy. CDH group and intervention group were given alcohol 2 ml. Results Incidence of teratogenesis caused by diaphragmatic hernia in intervention group was less than that in CDH group （46.34% vs 66.67%, P〈0.05 ）. Fetal rats in control group and CDH group showed similar lung development. The lung weight/body weight ratio, axial gland alveolus count （ RAC）, pulmonary alveolus area proportion and pulmonary alveolus area ratio in intervention group were significantly higher than those in CDH group [ （3.45 ±0.58） mg/g vs （2.36±0.61） mg/g, 4.4±0.3 vs 2.3 ±0.2, （63.7 ±5.6） % vs （46.5±7.3） %, （45±6） % vs （27±6.7） %, P 〈 0.01 ]. The alveolar septum area ratio in intervention group was significantly lower than that in CDH group [ （45±6.8）% vs （63 ±8.3 ）%, P 〈 0.01 ]. The mean media thickness percentage of pre-acinar pulmonary arteries and that of intra-acinar pulmonary arteries of fetal rats in intervention group were significantly lower than those in CDH group [ （22.1±2.2）% vs （24.3±4.0）%, （17.6±2.8）% vs （21.5±2.9）%, P 〈 0.01]. The proportion of non-muscle arteries in IAPA per unit of visual field in intervention group was significantly higher than that in CDH group [ （79.4±3.2） % vs （71.6±3.3） %, P 〈 0. 01 ]. Conclusions Prenatal treatment with vitamin E can decrease the incidence of CDH, which may improve the lung development and inhibit the vascular remodeling in lung.