【摘要】：目的觀察孕期葉酸缺乏對(duì)胎鼠生長(zhǎng)發(fā)育及胰島素樣生長(zhǎng)因子(IGF)系統(tǒng)甲基化的影響。方法將22只Sprague-Dawley雌鼠隨機(jī)分為葉酸缺乏組(n=12)和正常對(duì)照組(n=10),分別喂養(yǎng)葉酸缺乏飼料和普通飼料,2周后與雄鼠交配,兩組各8只雌鼠成功受孕,于懷孕第20天對(duì)孕鼠剖腹取胎,每組取32只胎鼠測(cè)量其頭尾長(zhǎng)、體重。兩組分別另取8只胎鼠,采用ELISA法對(duì)其腦、肝臟組織中的葉酸、IGF-1、胰島素樣生長(zhǎng)因子結(jié)合蛋白(IGFBP)-3水平進(jìn)行檢測(cè)。兩組分別另取3只胎鼠,使用全基因組甲基化測(cè)序方法檢測(cè)其腦、肝臟組織IGF系統(tǒng)的甲基化情況。同時(shí)采用ELISA法對(duì)兩組孕鼠血清IGF-1、IGFBP-3水平進(jìn)行檢測(cè)。結(jié)果葉酸缺乏組胎鼠頭尾長(zhǎng)、體重較正常對(duì)照組降低(P0.05);葉酸缺乏組孕鼠血清IGF-1、IGFBP-3與胎鼠腦、肝臟組織中的葉酸、IGFBP-3水平均低于正常對(duì)照組(P0.05);葉酸缺乏組胎鼠腦組織中IGF-1R、IGF-2R、IGFBP-2、IGFBP-5、IGFBP-6、IGFBP-7的甲基化水平均高于正常對(duì)照組(P0.05);而在肝臟組織中,相比于正常對(duì)照組,葉酸缺乏組胎鼠IGF-1R、IGF-2R、IGFBP-3、IGFBP-5甲基化水平增加,IGF-2甲基化水平則下降(P0.05)。結(jié)論孕鼠葉酸缺乏會(huì)影響胎鼠宮內(nèi)的生長(zhǎng)發(fā)育,其機(jī)制可能與胰島素生長(zhǎng)因子系統(tǒng)的甲基化異常有關(guān)。
[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.
【作者單位】： 四川大學(xué)華西第二醫(yī)院兒科/出生缺陷與相關(guān)婦兒疾病教育部重點(diǎn)實(shí)驗(yàn)室;
【基金】：國(guó)家自然科學(xué)基金(81330016;81270724;81630038) 四川省科技廳應(yīng)用基礎(chǔ)研究項(xiàng)目(2010JY0059);四川省科技廳基金(2014SZ0149;2016TD0002)
【分類號(hào)】：R714.2

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