为了揭示妊娠合并糖尿病诱发胚胎先天性神经管缺陷的分子机制,并探讨其有效的防治方法。实验选用6个实验组的Sprague Dawley大鼠:第1组为常规饲养的正常对照组;第2组尾静脉注射65mg/kgStreptozotocin(STZ)构建妊娠合并糖尿病、且诱发先天性神经管缺陷的实验组大鼠;第3组为STZ构建的糖尿病、但胚胎不伴有先天性神经管缺陷的大鼠模型;第4、5、6组为STZ构建的糖尿病治疗组大鼠,每日分别给予80μg/mL花生四烯酸(arachidonicacid,AA)、400mg维生素E、抗氧化剂(维生素E)和不饱和脂肪酸(safloweroil)混合物cocktail治疗。于妊娠第12天取出各组胚胎,解剖显微镜下进行形态学分析;提取卵黄囊细胞蛋白质,应用特异性抗磷酸化抗体进行免疫共沉淀及Western印迹,对MAP激酶信号途径上各蛋白激酶ERK1/2、JNK1/2、RAF 1活性进行分析。与正常对照组相比,妊娠合并糖尿病诱发的先天性神经管缺陷胚胎中(第2组),ERK1/2蛋白激酶活性显著下降,其上游RAF 1活性相应降低;与此相反,JNK1/2活性明显升高。在给予花生四烯酸、维生素E补充物治疗后,通过调节MAP激酶信号通路蛋白激酶活性,逆转了胚胎神经管缺陷的发生。妊娠合并糖尿病诱发的胚胎先天性神经管缺陷的发生,与MAP激酶信号传导机制异常密切相关。不饱和脂肪酸和抗氧化剂补充物的 In order to reveal the molecular mechanism of congenital neural tube defects induced by pregnancy associated with diabetes mellitus, and to explore its effective control methods. Six experimental groups were selected as Sprague Dawley rats: Group 1 was a normal control group; Group 2 was injected with 65 mg / kg Streptozotocin (STZ) through the tail vein to construct a group of experimental diabetes mellitus with congenital neural tube defects Rats in group 3 were STZ-diabetic rats, but embryos were not associated with congenital neural tube defects in rats. Groups 4, 5 and 6 were diabetic rats treated with STZ, and were given 80 μg / mL arachidonic acid (AA), 400 mg vitamin E, a cocktail of antioxidants (vitamin E) and unsaturated fatty acid (safloweroil). The embryos were removed on day 12 of gestation and morphological analysis was performed under a dissecting microscope. The protein of yolk sac cells was extracted and co-immunoprecipitated and Western blotted with specific anti-phosphorylation antibody. The expression of ERK1 / 2, JNK1 / 2, RAF1 activity were analyzed. Compared with the normal control group, ERK1 / 2 protein kinase activity was significantly decreased in congenital defects of neural tube defects induced by pregnancy complicated with diabetes (group 2), and the activity of RAF1 in the upstream decreased correspondingly. In contrast, JNK1 / 2 activity Significantly increased. After administration of arachidonic acid and vitamin E supplement, the occurrence of neural tube defects in embryos was reversed by regulating the activity of MAP kinase signaling pathway protein kinase. The occurrence of congenital neural tube defects induced by pregnancy complicated with diabetes is closely related to the abnormality of MAP kinase signal transduction mechanism. Unsaturated fatty acids and antioxidant supplements