环磷酰胺致神经管畸形及可能机理研究  

Experimental Study on Rats' Neural Tube Defects Caused by Cyclophosphamide and its Mechanism

作　　者：赵海峰[1] 肖荣[1] 杨燕[1] 邱服斌[1] 高竹琦[1] 李学敏[2] 

机构地区：[1]山西医科大学营养与食品卫生教研室,太原030001 [2]山西省疾病预防控制中心毒理科

出　　处：《中国公共卫生》2002年第11期1302-1304,共3页Chinese Journal of Public Health

基　　金：山西省自然科学基金 (2 0 0 1 1 0 62 )

摘　　要：目的　研究环磷酰胺致大鼠胚胎神经管畸形的作用及可能机理 ,并为其防治奠定基础。方法　将大鼠按体重随机分为正常对照组及 4个不同剂量的实验组 ,其剂量分别为 7 5 ,10 5 ,12 5和 15mg/kg ,均于孕 13天腹腔一次性注射相应剂量的环磷酰胺 ,于孕 14天各组随机处死 3只 ,胎鼠进行光镜形态学观察 ;其余动物均于孕 2 0天时处死 ,进行孕鼠血清生化指标的检测、胎鼠外形及病理检测和骨骼标本的观察。结果　胎鼠神经管畸形发生率及颅骨缺损、孕鼠血清的MDA、NO含量与环磷酰胺的剂量呈正相关 ;孕鼠血清的SOD、胎鼠的生长发育指标与剂量呈负相关 ;胎鼠畸形发生处有大量的凋亡细胞存在 ;以 12 5mg/kg的剂量组致畸率高且致死率低。 结论　利用环磷酰胺制备大鼠神经管畸形模型以 12 5mg/kg的剂量效果最佳 ;Objective To define the neural tube defects teratogenicity effects of cyclophosphamide and its mechanism on rats,provide basis for further study on prevention and cure.Methods The pregnant rats were randomly divided into control and four experimental groups according to their bodyweight,The cyclophosphamide intakes among five groups were 7\^5,10\^5,12\^5,15\^0mg/kg via intraperitoneal administration on the 13th day of gestation.On the 14th day of gestation,three rats were randomly killed and embryos were checked through optical microscopy;the other rats were killed on the 20th day of gestation,the biochemistry index and pathology slice were examined,the skeleton examples were made.Results The frequency of abnormalty,skull defects of embory and MDA?NO in serum of pregnant rats had significantly positive correlation with the intake of cyclophosphamide;while SOD and developmental index had significantly negative correlation.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 indicated some typical changes of apoptosis.Conclusion To make a model of neural tube defects,the intake of 12\^5mg/kg was feasible;oxidation and neurons apoptosis might be involved in its teratogenesis.

关 键 词：环磷酰胺 神经管畸形 氧化 细胞凋亡 NTDS 致畸机理 

分 类 号：R741[医药卫生—神经病学与精神病学]