神经管闭合的新见解:叶酸不应答型神经管畸形  

New Insights into Neural Tube Closure:Folic Acid Non-Responsive Neural Tube Defects

作　　者：任文彬 李建婷 解军 REN Wen-Bin;LI Jian-Ting;XIE Jun(Shanxi Key Laboratory of Birth Defect and Cell Regeneration,Department of Biochemistry and Molecular Biology,School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,China;MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学基础医学院生物化学与分子生物学教研室,出生缺陷与细胞再生山西省重点实验室,太原030001 [2]山西医科大学煤炭环境致病与防治教育部重点实验室,太原030001

出　　处：《中国生物化学与分子生物学报》2024年第5期575-587,共13页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.U23A20420,No.82201841);山西省基础研究计划(No.202203021212369);山西医科大学博士启动基金项目(No.SD2209,No.XD2116)资助。

摘　　要：神经管畸形(neural tube defects,NTDs)是一种常见的、严重且复杂的先天性畸形,是遗传、营养和环境因素相互作用的结果。母体妊娠期补充叶酸(folic acid,FA)已被证明是一种非常有效的策略,常用于部分NTDs的初级预防。然而,仍有一部分NTDs病例对FA治疗具有抵抗性,称为“FA不应答型NTDs”或“FA抵抗型NTDs”。FA不应答型NTDs的病因复杂,涉及遗传、营养、环境及母体相关因素。本文综述了叶酸不应答型NTDs的相关遗传、营养、环境及母体等风险因素,并揭示了其致病机制的研究进展。其中,遗传因素主要从小鼠突变体及品系、叶酸一碳代谢基因、关键凋亡基因三方面展开阐述,为该类患儿的产前诊断提供了可能的遗传检测位点。营养因素方面,本文主要聚焦目前已报道的肌醇和蛋氨酸,解释其对该种疾病潜在的干预机制,为NTDs患者早期营养干预提供新方向。此外,本文还探讨了叶酸一碳代谢中的辅助因子-维生素B12参与叶酸不应答型NTDs发生的可能机制,增加叶酸联合其他维生素治疗出生缺陷的可能性。最后,本文还综述了环境因素和母体因素在叶酸不应答型NTDs中的研究进展,为高危人群提供孕早期健康指导。总之,本文综述了叶酸不应答型NTDs的相关风险因素及其致病机制的研究进展,为当下该种疾病及同类型出生缺陷的防治提供新的见解。Neural tube defects(NTDs)are common,severe,and complicated congenital malformations that are the result of the interaction and interplay of genetic,nutritional,and environmental factors.Maternal periconceptional folic acid(FA)supplementation is a significantly effective strategy for primary prevention of a proportion of NTDs.However,there still exists a portion of NTD cases that are intrinsically resistant to FA therapies,which are widely referred to as“FA-non-responsive NTDs”or“FA-resistant NTDs”.These diseases have a complex etiology,involving genetic,nutritional,environmental and maternal factors.This review integrates the genetic,nutritional,environmental and maternal risk factors associated with FA non-responsive NTDs and reveals the progress of research on their pathogenic mechanisms.Among them,the genetic factors cover three aspects:mouse mutants and strains,FA one-carbon metabolism genes,and key apoptosis genes,which provide possible genetic testing loci for prenatal diagnosis of these children.Nutritional factors concentrate on the roles of inositol and methionine,delineating their possible mechanisms of action and suggesting new directions for early nutritional interventions in NTDs management.In addition,this paper explores the possible mechanisms by which vitamin B12,a cofactor in the FA one-carbon metabolism,in FA-non-responsive NTDs development.We posit that a combination of FA and other vitamins may enhance treatment strategies for these malformations.At last,this paper also reviews the influence of environmental and maternal factors on FA non-responsive NTDs,aiming to provide health recommendations for early pregnancy for at-risk populations.In summary,this article reviews and evaluates research advancement concerning FA non-responsive NTD risk factors and pathogenesis,providing novel insights into the current prevention and treatment of this disease and related birth defects.

关 键 词：神经管畸形 肌醇 小鼠模型 叶酸 卷尾 

分 类 号：Q7[生物学—分子生物学] R72[医药卫生—儿科]