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Abstract: The purpose of this study was to investigate the effect of 28vitamin B₁₂%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>vitamin B₁₂ on palatal development by co-administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dexamethasone (DEX). We examined the morphological and histological features of the palatal shelf and expression levels of key signaling molecules (28transforming growth factor-&beta%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>transforming growth factor-β283 (TGF-&beta%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>3 (TGF-β283)%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>3) and TGF-β type I receptor (activin receptor-like kinase 5, ALK5)) during palatogenesis among a control group (Group A), TCDD+DEX exposed group (Group B), and TCDD+DEX+28vitamin B₁₂%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>vitamin B₁₂ exposed group (Group C). While we failed to find that 28vitamin B₁₂%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>vitamin B₁₂ decreased the incidence of 28cleft palate%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>cleft palate induced by TCDD+DEX treatment, the expression levels of key signaling molecules (TGF-β3 and ALK5) during palatogenesis were significantly modulated. In TCDD+DEX exposed and TCDD+DEX+28vitamin B₁₂%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>vitamin B₁₂ exposed groups, palatal shelves could not contact in the midline due to their small sizes. Our results suggest that 28vitamin B₁₂%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>vitamin B₁₂ may inhibit the expression of some 28cleft palate%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>cleft palate inducers such as TGF-β3 and ALK5 in DEX+TCDD exposed mice, which may be beneficial against palatogenesis to some degree, even though we were unable to observe a protective role of 28vitamin B₁₂%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>vitamin B₁₂ in morphological and histological alterations of palatal shelves induced by DEX and TCDD.

维生素B12对四氯二苯并对二恶英和地塞米松联合诱导腭裂小鼠拮抗性的初步研究

研究目的：通过四氯二苯并对二恶英（TCDD）和地塞米松（DEX）联合致畸构建更稳定的腭裂动物模型，初步研究维生素B₁₂拮抗剂对腭突发育的影响，检测信号分子变化，为后续研究提供参考。
创新要点：TCDD和DEX联合致畸可建立更稳定、更具研究价值的腭裂小鼠模型。从腭裂发生率、腭突发育形态大小、中嵴上皮细胞形态以及转化生长因子-β3（TGF-β3）、受体活化样激酶5（ALK5）分子表达等不同层次初步探讨了维生素B₁₂的拮抗作用。
研究方法：在小鼠腭发育关键时期，采用高剂量TCDD和DEX一次给药建立模型，并观察维生素B₁₂的拮抗作用（见图3）。于胚胎期17.5天（GD 17.5）体视显微镜下检测各组腭裂发生率（见表1和图2），并于GD 13.5、GD 14.5、GD 15.5 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（见图4、5）。
重要结论：TCDD和DEX联合作用可诱导C57BL/6J胎鼠形成稳定腭裂。维生素B₁₂对联合致畸诱导的TGF-β3及ALK5表达的改变及腭突中嵴上皮细胞形态的改变有一定程度的抑制作用，对腭裂发生率及腭突发育形态大小改变尚无明显抑制作用。

关键词：腭裂；转化生长因子-β3；受体活化样激酶5；四氯二苯并对二恶英；地塞米松

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