砷对大鼠的致畸作用

目的进一步阐明砷对母体、胎儿、胚胎细胞的影响和验证体外致畸作用。方法用大鼠体内致畸法并结合扫描电镜、组织化学等技术深入探讨了砷的发育毒性和机制。结果Ａｓ２Ｏ３的各剂量组（０，１，４和１０ｍｇ／ｋｇ）均未见母鼠有明显的中毒症状和死亡；胎鼠死亡率分别为１０．２％，１７．４％，２４．８％和６１．１％；骨骼畸形率为１．８９％，３．１２％，１７．２８％和７８．５７％；染毒４８小时后的胚胎畸形率分别为３．１６％，５．３２％，１３．７９％和４０．４８％；扫描电镜观察可见多部位的胚胎表皮细胞受损，细胞表面和细胞连接处出现大小不一的空洞；胚胎畸形表现是神经管未闭、体位异常、肢芽小等；诱生型一氧化氮合成酶组化检查率先证明一氧化氮与胚胎发育异常关系密切，呈明显剂量－反应关系；活体染色表明砷能诱发肢芽细胞过度凋亡；从多角度分析了砷的致畸机理。结论大鼠体内试验证实，砷在胚胎生长发育过程中有致畸作用。

Teratogenic Effects of Arsenic on Rats

Objective To further clarify the effects of arsenic on pregnant rats, fetuses, fetal cells and to verify the experimental results in vitro, and to study the developmental toxicity and its mechanism of arsenic in depth. Methods Teratogenic methods in vivo combined with scanning electron microscopy and histochemical techniques were used in rats. Results No apparently toxic symptoms or deaths were observed in rats exposed to various doses of arsenic trioxide of 0, 1, 4 and 10 mg/kg. Fetal death rates in rats were 10.2%, 17.4%, 24.8% and 61.1%, proportions of skeletal deformity were 1 89%, 3.12%, 17.28% and 78.57%, and embryo deformity rates were 3.16%, 5.32%, 13.79% and 40.48% 48 hours after exposure, respectively for those exposed to various doses of arsenic. Damage in fetal epidermal cells and cavities of different size between cell surface and cell junction in multiple sites could be seen under scanning microscope. Dysrhaphia, body anomalies and small limb bud, etc. were main manifestation of embryo deformity. There was a close relationship between nitric oxide and anomalies in fetal development, with a dose response pattern, showed by inducible nitric oxide synthetase (iNOS) histochemical examinations. In vivo staining showed that excessive apoptosis could be induced by arsenic. And, teratogenic mechanisms of arsenic was analyzed in various ways. ConclusionArsenic has certain teratogenic effects on rats in vivo .