郑州大学学报（医学版）2025，Vol.60Issue(5)：623-627,5.DOI:10.13705/j.issn.1671-6825.2024.10.010
基于代谢组学分析Akt/mTOR通路在TCDD诱发胎鼠腭裂发生中的作用
Role of Akt/mTOR pathway in cleft palate generation of fetus mice based on metabolomic analysis
摘要
Abstract
Aim:To investigate the role of Akt/mTOR signaling pathway in cleft palate induced by 2,3,7,8-tetrachlo-rodibenzo-p-dioxin(TCDD)in fetal mice.Methods:C57BL/6N pregnant mice were randomly divided into TCDD group(n=15)and control group(n=15).On gestational day 10.5(GD10.5),the mice were intragastrically administered 64μg/kg TCDD or corn oil,respectively.Untargeted metabolomics detection was performed on palatal tissue of fetal mice in both groups on GD14.5,and KEGG and GO enrichment analyses were conducted for differentially accumulated metabolites.TUNEL staining was used to observe apoptosis of midline epithelial seam(MES)cells and mouse embryonic palatal mesen-chyme(MEPM)cells in fetal mice on GD14.5.Transmission electron was used to observe autophagy in palatal process cells of fetal mice on GD14.5.Western blot was used to detect the expressions of Akt,phosphorylated Akt(p-Akt),mTOR,phos-phorylated mTOR(p-mTOR),and autophagy-related proteins(LC3-Ⅱ/Ⅰ,Atg5,Beclin1,and P62).Results:Untargeted metabolomics analysis showed that differentially accumulated metabolites were related to multiple signaling pathways inclu-ding PI3K-Akt and mTOR.Compared with control group,the TCDD group showed increased apoptosis of MEPM cells and decreased apoptosis of MES cells(both P＜0.05).In the TCDD group,autophagosomes in MEPM and MES cells had irreg-ular morphology and reduced quantity;the expressions of LC3-Ⅱ/Ⅰ,Atg5,and Beclin1 were decreased,P62 expression was increased,and the expressions of p-Akt and p-mTOR proteins were increased(all P＜0.05).Conclusion:TCDD may acti-vate the Akt/mTOR pathway,inhibit autophagy of MEPM and MES cells,affect the process of cell apoptosis,thereby inter-fering with normal palatal development and ultimately leading to cleft palate.关键词
2,3,7,8-四氯二苯并对二噁英/腭裂/Akt/mTOR通路/代谢组学/小鼠Key words
2,3,7,8-tetrachlorodibenzo-p-dioxin/cleft palate/Akt/mTOR pathway/metabolomics/mouse分类
医药卫生引用本文复制引用
陈瑶,王威威,宋帅星,刘小转,余增丽,陶宇昌,纪鑫蓉,刘方..基于代谢组学分析Akt/mTOR通路在TCDD诱发胎鼠腭裂发生中的作用[J].郑州大学学报（医学版）,2025,60(5):623-627,5.基金项目
河南省自然科学基金项目(242300421494) （242300421494）
