环磷酰胺与同型半胱氨酸制备NTDs大鼠的比较

目的比较环磷酰胺和同型半胱氨酸两种致畸物质在建立大鼠神经管畸形模型中的作用.方法将大鼠按体重随机分为8组,即正常对照组、4个不同剂量的环磷酰胺组和3个不同剂量的同型半胱氨酸组,正常对照组给予生理盐水,环磷酰组的剂量分别为7.5,10.5,12.5和15 mg/kg,均于怀孕第13 d一次性腹腔注射相应剂量的环磷酰胺;同型半胱氨酸组的剂量分别为600,300和150mg/kg,于怀孕第1 d开始经口给药,每天1次,并持续整个怀孕期.各组孕鼠均于怀孕第14d随机处死3只,剖腹取胎鼠进行光镜形态学观察;其余孕鼠均于怀孕第20 d时处死,进行胎鼠外形、病理及电镜的检测.结果环磷酰胺组胎鼠神经管畸形发生处有大量的凋亡细胞存在;以12.5 mg/kg的剂量组致畸率高且致死率低;在本实验剂量范围内未发现同型半胱氨酸对大鼠的明显致神经管畸形的作用.结论可以利用12.5 mg/kg环磷酰胺制备大鼠神经管畸形模型;畸形的发生与胚胎神经管细胞过度凋亡有关;而大鼠对同型半胱氨酸没有对环磷酰胺致神经管畸形敏感.

Comparison study between cyclophosphamide and homocysteine to cause rat'''' s NTDs

Objective To comprise the neural tube defects teratogenicity effects of cyclophosphamide and homocysteine.Methods The pregnant rats were randomly divided into control and four cyclophosphamide experimental groups and three homocysteine experimental groups on their bodyweight.The cyclophosphamide intakes among four groups were 7.5,10.5, 12.5,15.0mg/kg via intraperitoneal administration on the 13th day of gestation,and the homocysteine intakes among three groups were 600,300,150mg/kg via mouth during pregnance.On the 14th day of gestation,three rats were randomly killed and embryos were checked through optical microscopy and transmission electron microscopy; The other rats were killed on the 20th day of gestation.Results The group of 12.5mg/kg had a high frequence of neural tube defects and a low frequence of death,the results from optical microscopy and transmission electron microscopy indicated some typical changes of apoptosis.But the positive teratogenicity effects of homocysteine on rats were not be observed in homocysteine experimental groups.Conclusion To make a model of neural tube defects,the intake of 12.5mg/kg was feasible;neurons apoptosis might be involved in its teratogenesis,while rat was not sensitivity to homocysteine.