文章摘要
李屾 梁良 姚志刚 王理 李睿 梁春联 刘驰.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[J].,2014,14(4):601-607
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
Fetal Mice Intrauterine Growth Retardation Induced by MmaternalFolate Deficiency and the Expression of Insulin-like Growth FactorSystemGenes in Fetal Hepatic Tissues
  
DOI:
中文关键词: 叶酸缺乏  宫内发育迟缓(IUGR)  胰岛素生长因子(IGF)
英文关键词: Folate Deficiency  Intrauterine Growth Retardation (IUGR)  Insulin-like Growth Factor (IGF)
基金项目:国家自然科学基金项目(81102117/H2603; 81000249/H0417)
作者单位
李屾 梁良 姚志刚 王理 李睿 梁春联 刘驰 北京大学首都儿科研究所教学医院
中国医学科学院医学实验动物研究所 
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中文摘要:
      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,分别饲以不含叶酸和含2 mg 叶酸/kg 的纯合饲料。四周后与雄 鼠交配,于怀孕第13.5 天(13.5 dpc)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-time PCR 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(IGFⅠ R)、胰岛素生长因子Ⅱ(IGF Ⅱ)、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,13.5 dpc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IGFⅡR mRNA 的相对表达水平均低于正常对照组 (P<0.05),IGFⅠ、IGFⅠR、IGFBP-1 和IGFBP-3 mRNA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IGFⅡR mRNA 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IUGR 发生机制有关。
英文摘要:
      Objective:Folic acid is a kind of water-soluble B vitamins, and it plays an important role in amino acid and nucleotide metabolism in vitro. 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) systemin 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 factorⅠ(IGFⅠ), insulin-like growth factorⅠ receptor (IGFⅠR), insulin-like growth factor Ⅱ (IGFⅡ ), insulin-like growth factorⅡ receptor (IGFⅡ R),insulin-like growth factor binding protein1 (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 of IGFⅡ and IGFⅡR 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 of IGFⅠ, IGFⅠR, 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 IGFⅡ and IGFⅡR genes of the fetal hepatic tissues.These results suggested that folate deficiency may regulate the expression of IGF genes, and take part in the mechanismof the occurrence of IUGR.
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