叶酸缺乏孕鼠子代脑组织DNA甲基化变化  

EFFECTS OF MATERNAL FOLATE DEFICIENCY ON DNA METHYLATION

作　　者：杨慧敏[1] 孙轶[2] 周天鸿[3] 廖国仪[1] 周冬[1] 余灵[1] 

机构地区：[1]暨南大学医学院第一附属医院儿科,广州510632 [2]广州医学院第二附属医院,510260 [3]暨南大学生命科学技术院

出　　处：《营养学报》2004年第3期187-191,共5页Acta Nutrimenta Sinica

基　　金：广东省自然科学基金资助项目(No.980700)

摘　　要：目的: 从分子水平探讨叶酸缺乏(FD)对胎鼠脑发育的影响。方法: 雌性SD大鼠实验组30只、对照组20只,分别饲以不含叶酸和含叶酸2 mg/kg的纯合饲料,2w后与雄鼠交配,于孕D20将孕鼠剖腹取胎,观察FD对胎鼠发育的影响,HPLC法检测孕鼠妊晚期末血清叶酸、胎鼠血清叶酸及胎鼠脑组织DNA甲基化水平。结果: (1)实验组孕鼠交配前及妊晚期末血清叶酸均明显低于对照组(P<0.01),外周血出现多分叶核粒细胞。实验组胎鼠血清叶酸也明显低于对照组(P<0.01),出现巨幼红细胞,RBC和Hb均低于对照组(P<0.01),且伴宫内生长迟缓。(2)实验组胎鼠脑组织DNA甲基化水平低于对照组(P<0.05),且与孕鼠及胎鼠的血清叶酸浓度呈正相关。结论: 母体FD时胎鼠的脑组织DNA甲基化水平降低,可能是胎鼠脑发育障碍的机制之一,受孕前后增补叶酸宜延长至妊娠结束。Objective: To verify the effect of maternal folate deficiency (FD)on fetal rat brain development, and the change of DNA methylation. Methods: Female Sprague-Dawley rats, 30 in the FD group and 20 in control group, received a purified diet without or with folate. After 14 d of feeding the rats were mated. The diets were provided continuously throughout gestation. On D20 of gestation the dams were killed, serum folate(SFA) and fetal development were observed. DNA methylation level in fetal brain was assayed by HPLC. Results:Dams in FD had significant lower SFA before mating or at the end of gestation than those in control group (P<0.01). Hypersegmented neutrophils were present in FD group(P<0.01). Fetal SFA in this group was lower than control too and all were associated with macrocytic anemia and intrauterine growth retardation. The DNA methylation level in fetal brain in FD group(P<0.05) was also lower than that in control group. SFA of dams and fetus and DNA methylation level in fetal brain were positively correlated. Conclusion:The decreased DNA methylation in fetal rat brain is possibly the mechanism of poor development of the fetal brain when the dams suffer from FD. So periconceptional folate supplementation should be prolonged to delivery.

关 键 词：叶酸缺乏 脑组织 DNA甲基化 孕鼠 胎鼠 

分 类 号：R151[医药卫生—营养与食品卫生学]