中文摘要：

目的建立四氯二苯对二恶英（TCDD）和地塞米松（DEX）联合诱导C57BL/6J小鼠腭裂模型,并在腭发育关键时期检测转化生长因子-β3（TGF-β3）和受体活化样激酶5（Alk5）基因的表达,探讨TCDD和DEX联合诱导胎鼠腭裂与TGF-β3和Alk5的相关性。方法在小鼠GD10～GD12,实验组小鼠连续3d胃饲TCDD和腹腔注射DEX,空白对照组不做处理,于GD17.5体视显微镜下检测各组腭裂发生率,并于GD13.5、GD14.5、GD15.5分别剪取胎鼠腭突提取RNA,采用实时荧光定量聚合酶链反应检测TGF-β3和Alk5基因表达。结果采用TCDD和DEX联合致畸,可诱导C57BL/6J胎鼠形成100%腭裂,建立了一种稳定适合分子生物学研究的腭裂动物模型。GD13.5时TGF-β3和Alk5基因表达水平在实验组与空白对照组之间差异均无统计学意义（P〉0.05）,在GD14.5、GD15.5实验组TGF-β3表达均降低（P〈0.05）,而Alk5表达均升高（P〈0.05）。结论 TCDD和DEX联合作用可诱导C57BL/6J胎鼠形成稳定腭裂,在腭融合关键时期诱导TGF-β3表达下降,Alk5表达升高,与腭裂的发生具有一定的相关性。

英文摘要：

Objective To establish a good animal model of cleft palate and confirm whether 2,3,7,8 tetrachloro-p-dibenzodioxin（TCDD） and Dexamethasone（DEX） induced palatal cleft in mice is related to the fold change of transforming growth factor-beta 3（TGF-β3） and activin receptor-like kinase 5（Alk5）.Methods Pregnant mice were treated with oral medication of TCDD and intraperitoneal injection with DEX on GD10-12 in experimental group while the control group without any treatment.Then embryos were examined on GD17.5 under stereomicroscope for calculating the incidence of cleft palate and palatal shelves were dissected from the staged embryos respectively for RNA extraction on GD13.5,GD14.5 and GD15.5.At last the real-time PCR and SYBR Green Ⅰ detection were used for RNA relative quantification.Results Cleft palate could be induced 100% in C57BL/6J fetal mice with TCDD and DEX,thus established a stable animal model for further molecular studies of cleft palate.There were no significant difference in expression level of TGF-β3 and Alk5 on GD13.5 among the groups,but the differences were statistically significant on GD14.5 and GD15.5（P〈0.05）.On the contrary,the expression level of Alk5 were significantly higher in experimental group（P〈0.05）.Conclusion Combined effects of TCDD and DEX could induce a stable formation of cleft palate and down-regulated mRNA of TGF-β3 and up-regulated Alk5 may contribute to the occurrence of cleft palate.