摘要
本实验选用雌性SD大鼠,妊娠第13天腹腔注射环磷酰胺(15mg/kg体重),分別于给药后4、8、12、24、48小时及妊娠第20天剖腹取胎,进行大体形态、光镜和透射电镜观察。结果显示环磷酰胺有明显的胚胎毒作用和致畸作用(致畸率为97.46％),神经管畸形较常见。在光镜下可见给药后8小时,神经上皮细胞开始变性、死亡,最早受影响的部位是端脑和后脑神经上皮的套层;给药后24小时损伤最重,范围广泛。电镜观察见线粒体、内质网等细胞器肿胀、溶解;单位膜模糊;细胞核固缩,电子密度增高。受损区域可见许多髓样小体、空泡、残余体等,神经管周围的间充质细胞排列紊乱,细胞死亡伴间质水肿。给药后48小时,吞噬细胞清除坏死组织并留下较大间隙。上述结果提示,环磷酰胺主要作用于DNA合成活跃的神经上皮细胞,并使其变性、死亡,还可引起线粒体等细胞超微结构的破坏;并能损伤神经管周围的间充质,干扰骨的发生过程。
In this paper, further study was made on the teratogenicity and the morphological teratogenesis mechanism of neural tube defects (NTD) caused by cyclophosphamide(CP). Pregnant SD rats were given single intraperitoneal injection of CP 15 mg/kg on day 13 of gestation. The fetuses were removed on day 20 of gestation, weighed and examined for external malformations. Some embryos were removed respectively at 4, 8, 12, 24, 48 hr after administration of CP, and examined with light microscope and electron microscope. The results showed that CP has obvious embryotoxie and teratogenic effects. Of the survivings, 97.46％ showed external malformations including encephalocele, exencephaly, opened eyes, micrognathia, limb and digital defects etc. We considered that the possible way by which CP caused the malformation on developing embryos may involve the following aspects: (1) CP caused DNA-synthesising cells to degenerate and become necrosis. (2) The cellular organelle (mitochondria and endoplasmic reticulum, etc.) became irregular in shape and fragmented. (3) The mesenchyme surrounding the neural tube were also damaged by CP and therefore influenced the skull ossification.
出处
《解剖学报》
CAS
CSCD
北大核心
1990年第1期107-110,共4页
Acta Anatomica Sinica
基金
国家自然科学基金
关键词
环磷酰胺
致畸作用
神经管畸形
Cyclophosphamide
Teratogenic effect
Neural tube defect
Rats
