二恶英对成骨细胞胰岛素样生长因子家族基因表达的抗雌激素作用  

Antiestrogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the gene expression of insulin-like growth factors family in osteoblast cells

作　　者：郭磊[1] 赵彦艳[2] 董凌月[2] 丁茜[2] 孙开来[2] 吉世俊[3] 王绿增[4] 

机构地区：[1]中国医科大学附属第一医院骨科,沈阳110001 [2]中国医科大学附属第一医院医学遗传学教研室,沈阳110001 [3]中国医科大学附属第二临床医学院小儿骨外科,沈阳110001 [4]中国医科大学附属第二临床医学院动物部,沈阳110001

出　　处：《中华医学遗传学杂志》2003年第6期490-494,共5页Chinese Journal of Medical Genetics

基　　金：科技部 973资助项目 (0 0 1CB510301 );辽宁省教育厅高等学校科学研究项目资助 (20 2013172)~~

摘　　要：目的　探讨大鼠骨骼发育过程中环境类致畸因子对成骨细胞中胰岛素样生长因子 (insulin- likegrowth factors,IGFs)家族基因表达的抗雌激素作用。　方法　应用环境类致畸因子二恶英 (2 ,3,7,8-tetrachlorodibenzo- p- dioxin,TCDD)构建先天性大鼠骨骼发育畸形动物模型 ;应用雌激素和 TCDD分别或联合作用于小鼠头盖骨成骨样 (MC- 3T3- E1)细胞株 ;再用逆转录 -聚合酶链反应及流式细胞仪定量检测胎鼠头盖骨组织和 MC- 3T3- E1细胞中 IGF- 和胰岛素样生长因子结合蛋白 - 6 (insulin- like growth factor bindingprotein- 6 ,IGFBP- 6 ) m RNA的表达和细胞增殖率。　结果　在 5～ 15 μg/ kg TCDD浓度下诱导了大鼠骨骼发育畸形 ,并存在剂量依赖性生物学效应 ;雌激素增加了胎鼠头盖骨组织及 MC- 3T3- E1细胞中 IGF- m RNA的表达 ,提高了 MC- 3T3- E1细胞的增殖率 ,但使 IGFBP- 6 m RNA的表达降低 ;TCDD抑制了雌激素对 IGF- 、IGFBP- 6基因表达及细胞增殖的调节作用。　结论　在高雌激素水平下 ,TCDD可以诱导大鼠骨骼发育畸形 ;通过靶基因 IGF- 和 IGFBP- 6 ,TCDD可发挥拮抗雌激素对成骨细胞的正性调节作用。Objective To investigate the antiestrogenic effect of environment teratogen on the gene expression of insulin-like growth factors(IGFs) family in osteoblast cells during rat skeleton development. Methods The fetal rat models with congenital skeleton malformation were constructed by treating 20 female Wistar rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on pregnant day 10. The MC-3T3-E1 cells were cultured with estrogen, TCDD, or a combination of the two chemicals for 24 hours. The IGF-Ⅱ and IGFBP-6 mRNA levels in rat calvaria bone tissue and MC-3T3-E1 cells were detected by reverse transcription-polymerase chain reaction. Flow cytometer was used to determine the cell proliferation. Results TCDD at the concentration of 5-15 μg/kg induced developmental skeleton defect of fetal rat, and the effect was dose-dependent. The expression of IGF-Ⅱ mRNA gene was enhanced by estrogen in rat calvaria bone tissue and MC-3T3-E1 cells, whereas IGFBP-6 mRNA was decreased. Estrogen increased the cell proliferation in MC-3T3-E1 cells. TCDD, however, inhibited the effect of estrogen on regulation of IGF-Ⅱ gene and IGFBP-6 gene as well as MC-3T3-E1 cell proliferation. Conclusion These findings provide the evidence that TCDD can induce congenital fetal skeleton malformation under the condition of high estrogen level in pregnant Wistar rats. TCDD has antiestrogenic effect and hence exerts negative influence on the osteoblast cells through target IGF-Ⅱ and IGFBP-6 of IGFs family.

关 键 词：二恶英 成骨细胞 胰岛素样生长因子 基因表达 抗雌激素作用 先天性骨骼发育畸形 

分 类 号：R363[医药卫生—病理学]