叶酸缺乏致胎鼠宫内发育迟缓及肝脏胰岛素生长因子系统表达变化

目的：叶酸是一种水溶性B族维生素，在体内氨基酸与核苷酸代谢中起重要作用，是胎儿生长发育所必须的营养素。本文通过建立叶酸缺乏的孕鼠模型，探讨叶酸缺乏对胎鼠宫内发育的影响，并研究胎鼠肝脏组织中胰岛素生长因子（IGF）系统的表达变化。方法：雌性C57BL／6J小鼠叶酸缺乏组6只、正常对照组6只，分别饲以不舍叶酸和含2mg叶酸／kg的纯合饲料。四周后与雄鼠交配，于怀孕第13．5天（13．5dpc）对孕鼠剖腹取胎，观察和评价胎鼠发育指标，并对宫内发育迟缓（IUGR）比率进行统计。用Real-timePCR法检测胎鼠肝脏组织中胰岛素生长因子I（IGFI）、胰岛素生长因子I受体（IGFIR）、胰岛素生长因子II（IGFII）、胰岛素生长因子II受体（IGFIIR）、胰岛素生长因子结合蛋白1（IGFBP-1）和胰岛素生长因子结合蛋白3（IGFBP-3）mRNA的相对表达水平。结果：叶酸缺乏组雌鼠合笼前每日体重增长量降低，13．5dpc胎鼠吸收胎和死胎比率升高，胎重下降，IUGR比率显著升高，差异有统计学意义（P〈0．05）；叶酸缺乏组胎鼠肝脏组织中IGFII和IGFIIRmRNA的相对表达水平均低于正常对照组（P〈0．05），IGFI、IGFIR、IGFBP-1和IGFBP-3mRNA的相对表达水平两组间没有差异（P〉0．05）。结论：叶酸缺乏会导致小鼠孕中期胎鼠IUGR比率升高及胎肝IGFII和IGFIIRmRNA的表达水平降低，提示叶酸缺乏对IGF系统基因的调控，可能与胎鼠I-UGR发生机制有关。

Fetal Mice Intrauterine Growth Retardation Induced by Mmatemal Folate Deficiency and the Expression of Insulin-like Growth Factor System Genes in Fetal Hepatic Tissues

Objective： Folic acid is a kind of water-soluble B vitamins, and it plays an important role in amino acid and nucleotide metabolism in vivo. It is an essential nutrient for fetal growth. The aim of our study is to explore the effects of folate deficiency on fetal growth of mice, and the expressions of Insulin-like Growth Factor（IGF） system in fetal hepatic tissues through a pregnant mouse model of folate deficiency. Methods： Female C57BL/6J mice, 6 in the folate deficient group and 6 in the control group, are received a purified diet without or with folate 2 mg Per kg diet. Dams were mated after 4 weeks of feeding. The diets were continued throughout gestation. On day 13.5 of gestation the dams were killed, fetal growth was observed and assayed, and Intrauterine Growth Retardation （IUGR） rate was calculated. The expressions of insulin-like growth factor I （IGF I ）, insulin-like growth factor I receptor （IGF I R）, insulin-like gro- wth factor II （IGF II ）, insulin-like growth factor II receptor （IGF II R）,insulin-like growth factor binding proteinl （IGFBP-1） and insulin-like growth factor binding protein3 （IGFBP-3） mRNA at 13.5 dpc of fetal hepatic tissue were evaluated by Real time RT-PCR. Results： The body weight gain per day of maternal mice in folate deficient group was lower than in control group, and the 13.5 dpc fetal weight in folate deficient group was also lower （P〈0.05）. The number of absorbed and dead fetus and the IUGR rate in folate deficient group was higher than those in control group （P〈0.05）. The expressions oflGF II and IGF II R genes mRNA of the study group were significantly weaker than those of the control group in hepatic tissue of the 13.5 day fetuses （P〈0.05）, but there were no difference between the expression oflGF I, IGF I R, IGFBP-1 and IGFBP-3 of two groups（P〉0.05 ）. Conclusion： Folate deficiency may inhibit the fetal growth and elevate IUGR rate, and negatively modulates the expressions of IGF II and IGF II R genes of the fetal hepatic tissues. These results suggested that folate deficiency may regulate the expression oflGF genes, and take part in the mechanism of the occurrence of IUGR.