孕鼠叶酸缺乏对子鼠胰岛素样生长因子系统甲基化的影响

发布时间：2018-08-11 15:49

【摘要】：目的观察孕期叶酸缺乏对胎鼠生长发育及胰岛素样生长因子(IGF)系统甲基化的影响。方法将22只Sprague-Dawley雌鼠随机分为叶酸缺乏组(n=12)和正常对照组(n=10),分别喂养叶酸缺乏饲料和普通饲料,2周后与雄鼠交配,两组各8只雌鼠成功受孕,于怀孕第20天对孕鼠剖腹取胎,每组取32只胎鼠测量其头尾长、体重。两组分别另取8只胎鼠,采用ELISA法对其脑、肝脏组织中的叶酸、IGF-1、胰岛素样生长因子结合蛋白(IGFBP)-3水平进行检测。两组分别另取3只胎鼠,使用全基因组甲基化测序方法检测其脑、肝脏组织IGF系统的甲基化情况。同时采用ELISA法对两组孕鼠血清IGF-1、IGFBP-3水平进行检测。结果叶酸缺乏组胎鼠头尾长、体重较正常对照组降低(P0.05);叶酸缺乏组孕鼠血清IGF-1、IGFBP-3与胎鼠脑、肝脏组织中的叶酸、IGFBP-3水平均低于正常对照组(P0.05);叶酸缺乏组胎鼠脑组织中IGF-1R、IGF-2R、IGFBP-2、IGFBP-5、IGFBP-6、IGFBP-7的甲基化水平均高于正常对照组(P0.05);而在肝脏组织中,相比于正常对照组,叶酸缺乏组胎鼠IGF-1R、IGF-2R、IGFBP-3、IGFBP-5甲基化水平增加,IGF-2甲基化水平则下降(P0.05)。结论孕鼠叶酸缺乏会影响胎鼠宫内的生长发育,其机制可能与胰岛素生长因子系统的甲基化异常有关。
[Abstract]:Objective to observe the effects of folic acid deficiency during pregnancy on growth and development of fetal rats and methylation of insulin-like growth factor (IGF) system. Methods Twenty-two Sprague-Dawley female rats were randomly divided into folic acid deficiency group (n = 12) and normal control group (n = 10). They were fed folic acid deficiency diet and normal diet forage for 2 weeks to mate with male rats. Eight female rats in each group were successfully conceived, and the pregnant rats were taken out by caesarean section on the 20th day of pregnancy. The head and tail length and body weight of 32 fetal rats were measured in each group. The levels of folate IGF-1 and insulin-like growth factor-binding protein (IGFBP)-3) in brain and liver were determined by ELISA method. The methylation of IGF system in brain and liver was detected by whole genome methylation sequencing method in three other fetal mice. At the same time, the serum IGF-1 and IGFBP-3 levels of pregnant rats were detected by ELISA method. Results the fetal rats of folic acid deficiency group had longer head and tail length and lower body weight than the normal control group (P0.05), and the serum IGF-1IGFBP-3 and fetal brain in the folic acid deficiency group were significantly lower than those in the normal control group. The level of IGFBP-3 in liver tissue was lower than that in normal control group (P0.05), and the methylation level of IGF-1RnIGFBP-2IGFBP-2 IGFBP-5 IGFBP-6 IGFBP-7 in fetal brain tissue of folate deficiency group was higher than that of normal control group (P0.05), while in liver tissue, the methylation level of IGFBP-2 IGFBP-2 IGFBP-5 and IGFBP-6 IGFBP-7 was significantly higher than that of normal control group (P0.05). In folic acid deficiency group, the IGF-1RN IGF-2RN IGFBP-3IGFBP-5 methylation level increased and IGF-2 methylation level decreased (P0.05). Conclusion folic acid deficiency in pregnant rats may affect the growth and development of fetal rats, and its mechanism may be related to abnormal methylation of insulin growth factor system.
【作者单位】：四川大学华西第二医院儿科/出生缺陷与相关妇儿疾病教育部重点实验室;
【基金】：国家自然科学基金(81330016;81270724;81630038) 四川省科技厅应用基础研究项目(2010JY0059);四川省科技厅基金(2014SZ0149;2016TD0002)
【分类号】：R714.2

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