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大鼠孕期接受乙撑硫脲治疗后的神经细胞变性与子代存活情况

Nerve cell degeneration and progeny survival following ethylenethiourea treatment during pregnancy in rats.

作者信息

Khera K S, Tryphonas L

出版信息

Neurotoxicology. 1985 Fall;6(3):97-102.

PMID:4047519
Abstract

Ethylenethiourea (ETU)-induced early histologic changes in fetal CNS and their effect on postnatal survival was studied at 0, 15 or 30 mg/kg administered as single oral dose on day 13 of pregnancy. Fetuses, from 4-6 dams killed at post-treatment intervals of 12, 24, 48 and 72 h were fixed and studied for histopathological changes following routine methods. The remaining dams were allowed to litter and their progeny was studied for postnatal survival until 80 days of age. Histologic study revealed the presence of karyorrhexis in the germinal layer of basal lamina of CNS extending from the thoracic spinal cord to the telencephalon twelve hours after treatment with 30 mg of ETU/kg. At 48 h post-treatment, the spinal cord showed obliteration and duplication of the central canal and disorganization of germinal and mantle layers. In the brain, the ventricular lining was focally denuded, neuroepithelial cells were arranged in the form of rosettes and the nerve cell proliferation was disorganized. In the 15 mg of ETU/kg group, cellular necrosis was less severe and consisted of degeneration in a single or a small group of cells widely dispersed in the germinal layer of neuraxis. The initial degenerative changes were observed in a specific nerve cell type, identified as the undifferentiated migrating neuroblast. In the postnatal study, since survival was reduced to 50% at the 30 mg/kg and unaffected at the 15 mg/kg, it was concluded that necrosis of neuroblasts up to a certain degree was compatible with postnatal life until adulthood.

摘要

研究了在妊娠第13天以0、15或30毫克/千克的单次口服剂量给予乙撑硫脲(ETU)后,其对胎儿中枢神经系统(CNS)早期组织学变化的影响以及对出生后存活的影响。在治疗后12、24、48和72小时的不同时间点处死4至6只母鼠,取出胎儿进行固定,并按照常规方法研究其组织病理学变化。其余母鼠正常产仔,并对其后代进行出生后存活情况的研究,直至80日龄。组织学研究显示,在用30毫克ETU/千克治疗12小时后,中枢神经系统基底层生发层出现核碎裂,范围从胸段脊髓延伸至端脑。治疗后48小时,脊髓中央管出现闭塞和重复,生发层和套层结构紊乱。在大脑中,脑室衬里局部剥脱,神经上皮细胞呈玫瑰花结样排列,神经细胞增殖紊乱。在15毫克ETU/千克组中,细胞坏死程度较轻,表现为单个或一小群细胞的变性,广泛分布于神经轴突生发层。最初的退行性变化在一种特定的神经细胞类型中观察到,被确定为未分化的迁移神经母细胞。在出生后研究中,由于30毫克/千克组的存活率降至50%,而15毫克/千克组未受影响,因此得出结论,神经母细胞坏死在一定程度内与成年前的出生后生活是相容的。

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