二噁英致大鼠先天骨骼发育畸形中软骨细胞的病理学改变

目的探讨大鼠骨骼发育过程中环境类致畸因子对大鼠骨骼发育的先天性致畸作用。方法应用不同剂量的环境类致畸因子-二噁英（2，3，7，8-tetrachlorodibenzo-p-dioxin，TCDD）构建先天性Wistar大鼠骨骼发育畸形动物模型；茜素红染色法制作并观察透明骨骼标本；采用光镜和透射电镜观察胎鼠趾骨骨化中心的软骨细胞病理学变化及细胞超微结构的改变。结果TCDD在5～15μg／kg浓度下诱导了大鼠骨骼发育畸形，畸形包括：内翻足、脊柱裂、腭裂、无尾畸形等，并存在剂量依赖性生物学效应；光镜下可见在畸形胎鼠的肢端骨化中心软骨发生带缩小，软骨细胞变性。透射扫描电镜下见软骨细胞核内粗面内质网扩张，核基质降解，线粒体嵴不规则。结论在高雌激素水平下，TCDD可以诱导大鼠骨骼发育畸形；TCDD可能通过干扰软骨细胞的形态和功能代谢，引起原发性骨化中心的结构紊乱而发挥骨骼致畸效应。

Pathological Changes of Chondrocytes in Rats with Dioxin-Induced Congenital Skeletal Malformation

Objective To investigate the teratogenic effect of enviromental teratogen dioxin on rat skeletal development. Methods Fetal rat models with congenital skeleton malformation were constructed by treating Wistar rats with 2, 3,7, 8- tetrachlorodibenzo-p-dioxin （TCDD） on pregnancy day 10. The transparent skeleton of fetal rat was stained with alizarin Bordeaux. The histopathological and ultrastructural change of chondrocytes in ossification center of fetal rat were examined by light and transmission electron microscopy. Results Treated with 5 - 15 μg/kg TCDD, single or multiple skeletal developmental malformation in the fetal rats were induced. The abnormalities included crossfoot, skull growth flaw, cleft palate and taillessness. TCDD induction of the skeletal malformation was dose-dependent. There were degeneration of chondrocyte s and decreased ossification center in fetal extremity limbs. Ultrastructural changes in chondrocytes included dilatation of rough endoplasmic reticulum, pale nuclear matrix, damage of mitochondrial cristae, and so on. Conclusion Our findings provided evidence that TCDD can induce congenital fetal skeleton malformation under the conditions of high estrogen level in pregnant Wistar rats. TCDD has teratogenic effect on rat fetal skeletal development showing structural and functional damage to chondrocytes and primary ossification center.