Abstract: Objective To study the animal model of neural tube defects (NTDs) induced by cyclophosphamide (CD) in mice, and to explore the protective effects of taurine and its mechanism, and provide a theoretical basis on the prevention of human NTDs. Methods NTDs model was set up in mouse embryo by CP.The mouse embryonic neural tube development situation and the abnormal situation in each group was analysised and compared.Immunohistochemistry and image analysis technology were used to detected the expression of Cx26 and Cx43 protein in each group of mouse embryonic neural tube epithelial cells.Its relationship was analyzed with NTDs happening. Results 1)The best dose was 15 mg/kg body weight to establish the model of NTDs in mice with CP.Taurine could effectively reducing the occurrence of NTDs.2)Cx26 and Cx43 proteins were localized in the cell membrane and cytoplasm in nerve cells.The expressions of Cx26 and Cx43 proteins in CP group were significantly higher than those in the control group (P＜0.05).The expressions of Cx26 and Cx43 proteins in middle and high dosage taurine group were decreased significantly (P＜0.05). Conclusions Excessive expressions of Cx26 and Cx43 might be one of the important causes of NTDs with cyclophosphamide.Taurine can antagone the toxicity of cyclophosphamide and protect nerve cells, witch may reduce the occurrence of NTDs.

Key words: cyclophosphamide, neural tube defects, taurine , Connexin26, Connexin43

摘要： 目的 研究环磷酰胺(cyclophosphamide, CP)引起小鼠神经管畸形(neural tube defects, NTDs)的动物模型, 探讨牛磺酸的保护作用及其作用机理, 为预防NTDs的发生提供理论依据。方法 建立CP致小鼠NTDs模型, 分析比较各组鼠胚神经管发育情况和畸形情况;用免疫组织化学和图像分析技术检测各组鼠胚神经管上皮细胞中Cx26和Cx43蛋白的表达, 分析其与NTDs发生的关系。结果 1)用CP建立小鼠NTDs模型的最佳剂量为15 mg/kg体重, 牛磺酸能有效减少NTDs的发生;2)Cx26和Cx43蛋白定位于神经细胞的胞膜和胞质, CP组Cx26和Cx43蛋白的表达明显高于对照组(P＜0.05);中、高剂量牛磺酸组Cx26和Cx43蛋白的表达显著降低(P＜0.05)。结论 Cx26和Cx43的过度表达可能是CP致NTDs的途径之一;牛磺酸可能拮抗CP的毒性, 保护神经细胞, 减少NTDs的发生。

关键词: 环磷酰胺, 神经管畸形, 牛磺酸, Cx26, Cx43