【作者】 肖文林；

【导师】 石冰；

【作者基本信息】 四川大学 ， 口腔临床医学， 2006， 博士

【摘要】 背景和目的：非综合征性唇裂伴或不伴腭裂(Nonsyndromic cleft of the lip and／or palate，NCL／P)是常见的出生缺陷，是一种多基因易感性疾病，有着复杂的遗传特点，目前研究认为非综合征唇腭裂的发生是遗传和环境共同作用的结果，倾向于是继发的基因—环境因素相互作用而形成的。5，10—亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reducetase，MTHFR)在叶酸代谢中起重要作用，其功能为催化5，10—亚甲基四氢叶酸还原为5—亚甲基四氢叶酸。MTHFR基因突变可导致酶活力降低，使娩出的胎儿出现畸形，并且MTHFR基因敲除小鼠表现为包括唇腭裂在内的颅面畸形。作为环境因素之一的包括叶酸在内的多维生素孕早期的补充可以降低先天性唇腭裂的发生的危险。动物实验证实MTHFR基因活性丧失产生唇腭裂畸形，流行病学调查认为MTHFR基因突变的人群补充叶酸可以预防胎儿唇腭裂的发生率。但是叶酸预防MTHFR基因突变致畸作用的机制并不清楚，本文应用RNA干扰技术从细胞水平对MTHFR基因突变致畸作用机制及补充叶酸拮抗MTHFR基因下调作用的机制进行了研究。方法：首先，应用构建的MTHFR基因沉默载体对原代培养的C57BL／6J近交系小鼠的胚胎更多还原

【Abstract】 Objective: Nonsyndromic CLP is composed of two separate entities: cleft lip and palate (CL±P) and cleft palate only (CPO). Cleft lip (CL) with or without cleft palate (CP; CL/P) ranks among the most common birth defects in humans. Our understanding of aetiology and pathogenesis of these birth defects, particularly the non-syndromic variants, remains relatively poor. This is due to the complexity and diversity of the mechanisms through genetic and environmental factors involved in embryogesis Methylenetetrahydrofolate reductase (MTHFR) maps on the chromosome 1q36 and is a key enzyme of folic acid metabolism. MTHFR knockout mice appearance craniofacial deformity, including NCL/P. Because MTHFR is a key enzyme in folate metabolism, there is evidence that maternal use of a multivitamin with folic acid in early pregnancy reduces the risk of NCL/P. Observational studies suggest that multivitamins may reduce the risk of clefts . Mothers carrying the MTHFR 677TT genotype and更多还原