叶酸对IUGR大鼠胎盘VEGF及其受体1表达的影响

摘要：目的　观察叶酸对宫内发育迟缓（IUGR）大鼠胎盘中血管内皮生长因子（VEGF）及其受体1（Flt1）表达的影响和对胎鼠发育迟缓的治疗效果。方法　将20只雌性Wistar大鼠随机均分成4组：正常对照（N）组，正常饮食；IUGR组，妊娠期给予低蛋白饮食；叶酸+IUGR（A+IUGR）组，交配前2周至妊娠期给予叶酸每日2.0 mg/kg灌胃处理，受孕成功后妊娠期给予低蛋白饮食；叶酸+正常对照（A+N）组，交配前2周至妊娠期给予叶酸每日2.0 mg/kg灌胃处理，正常饮食。各组孕鼠在孕20 d时剖宫产取胎鼠，观察每组胎鼠体质量、胎盘质量、胎盘系数的变化，采用免疫组化染色和Western blot检测胎盘VEGF和Flt1蛋白表达，qPCR检测胎盘VEGF和Flt1 mRNA表达。结果　与N组相比，IUGR组的胎鼠体质量、胎盘质量、胎盘系数均明显降低，且胎盘中VEGF和Flt1的表达明显降低（P＜0.05）。A+IUGR组较IUGR组胎盘质量、胎盘系数显著增加（P＜0.05），A+IUGR组胎盘组织中VEGF和Flt1表达明显高于IUGR组（P＜0.05）。结论　叶酸可以通过上调IUGR大鼠胎盘中VEGF及Flt1的表达，进一步提高胎盘血管密度，从而促进胎盘和胎鼠发育，降低IUGR子代不良结局的发生风险。

Effects of folic acid on expression of VEGF and receptor 1 in placenta of IUGR rats

Abstract: Objective　To observe the effects of folic acid on the expression of vascular endothelial growth factor (VEGF) and receptor 1 (Flt1) in placenta of intrauterine growth retardation (IUGR) rats, and the therapeutic effect on fetal development. Methods　Female Wistar rats (n=20) were randomly divided into four groups: the normal control group (N, normal diet), the IUGR group (low protein diet was given during pregnancy), the folic acid + IUGR group (A+IUGR, folic acid 2.0 mg·kg-1·d-1 was given from two weeks before mating to pregnancy, low protein diet was given during pregnancy after successful conception), and the folate + normal control group (A+N, 2.0 mg·kg-1·d-1 folic acid was administered by gavage from 2 weeks before copulation during pregnancy). After successful conception, normal diet was given during pregnancy.Fetal rats were collected by cesarean section at 20 days after pregnancy. Immunohistochemistry, qPCR and Western blot assay were used to detect the mRNA and protein expressions of VEGF and Flt1 in placenta. Results　Compared with the normal group, the fetal body weight, placental mass and placental coefficient were significantly decreased in the IUGR group, and the expression levels of VEGF and Flt1 in placenta were significantly decreased. The placental mass and placental coefficient were significantly increased in the A+IUGR group compared with that of the IUGR group (P＜0.05), and the expression levels of VEGF and Flt1 in placenta were significantly higher in the A+IUGR group than those of the IUGR group (P＜0.05). Conclusion　Folic acid can further improve the placental vascular density by enhancing the expression of VEGF and Flt1 in placenta of IUGR rats, so as to promote the development of placenta and fetal mice, and reducing the adverse pregnancy outcome of IUGR offspring.