摘要
目的:总结归纳2,3,7,8-四氯二苯二英(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)诱导胎鼠腭裂的实验研究现状,为深入探讨TCDD致胎鼠腭裂的发生机制提供新的思路。方法:通过中国知网、NCBI等国内外文献库检索"TCDD""腭裂"等关键词,搜集已有文献资料。结果:目前的资料显示,可以通过约20μg/kg剂量的TCDD给予孕第9~14天的小鼠单次灌胃建立稳定的胎鼠腭裂模型。在此基础上发现,TCDD诱导不涉及腭突体积变化,主要通过抑制腭突接触融合而发挥致腭裂效应。对于发育中的腭组织细胞,TCDD能改变一系列调节细胞增殖、分化、凋亡的生长因子及其受体的表达,主要包括表皮细胞生长因子(epidermal growth factor,EGF)、转化生长因子(transforming growth factor,TGF)、芳香烃受体(aryl hydrocarbon receptor,AhR)。这些分子的表达变化尚存在争议。腭融合过程中发挥关键作用的腭中缝上皮细胞(medial edge epithelium,MEE),其细胞命运转归尚未阐明。结论:TCDD诱导胎鼠腭裂的体内实验基础相对完善。腭发育调控机制纷繁复杂,注重器官发育的时空动态性对于进一步研究至关重要。腭器官离体培养将是重要的体外实验环节。实验技术和条件的变革对于本领域的研究进展显得愈加迫切。
Objective:To summarize the experimental research progress on murine cleft palate induced by 2,3,7,8-tetrachlorodibenzop-dioxin(TCDD) and to provide new thoughts for further mechanisms in TCDD-induced murine cleft palate.Methods:Literatures from domestic and foreign database including CNKI and NCBI were reviewed,searching the keywords of "cleft palate""TCDD",etc.Results:Data up till now showed that a stable fetal cleft palate model could be established by treating pregnant mice with a single oral administration of approximate 20 μg/kg of TCDD from gestation day 9 to 14.Palate size altering was not involved in this model.TCDD inhibited palate contact and fusion to induce fetal cleft palate.TCDD altered the expression of a series of growth factors and receptors including epidermal growth factor(EGF),transforming growth factor(TGF) and aryl hydrocarbon receptor(Ah R) which could regulate cell proliferation,differentiation and apoptosis in palate tissue.Expression alterations of these molecules were still controversial.The cell fate of medial edge epithelium(MEE)which was vital to palate fusion was still not clear.Conclusion:The basis of studies in vivo on TCDD-induced fetal cleft palate is comparatively refined.Regulation mechanisms in palatal devel opment are complicated.It is crucial to notice the space-time dynamics in organgenesis in further research.Culture of palate organ will be an important part of studies in vitro.Revolution of experimental technique and condition appears even more necessary and urgent for research progress in this field.
引文
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