安徽医科大学学报2026，Vol.61Issue(2)：225-232,8.DOI:10.19405/j.cnki.issn1000-1492.2026.02.006
α-酮戊二酸经PI3K/AKT改善砷诱导的子代肝脂质沉积
α-ketoglutarate ameliorated arsenic-induced hepatic lipid deposition in offspring via PI3K/AKT signaling pathway
摘要
Abstract
Objective To investigate the protective effect of α-ketoglutarate(α-KG)on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy.Methods 8-week-old institute of cancer research(ICR)mice were mated in a ratio of 2∶1 between females and males,and the detection of vaginal plugs confirmed preg-nant.A total of 32 pregnant mice were randomly divided into four groups:control group,arsenic group,α-KG group,arsenic+α-KG group.On gestational day 0-16(GD0-GD16),the arsenic and arsenic+α-KG groups were ex-posed to sodium arsenite(NaAsO2,15 mg/L)in drinking water everyday,and the α-KG and arsenic+α-KG groups were gavaged with α-KG(2 g/kg)everyday.On GD16,pregnant mice were euthanized to collect fetal liver,and fe-tal body weight and crown-rump length were measured.Gene expression differences between the control group and the arsenic group were analyzed by transcriptome.The total triglycerides(TGs)and subtypes in fetal liver were de-tected by liquid chromatography tandem mass spectrometry(LC-MS/MS).Oil red O staining was used to observe the histopathological changes in the liver.Quantitative polymerase chain reaction(qPCR)was used to detect the expression level of genes related to lipid synthesis,transport,and degradation,and phosphatidylinositol 3'-kinase/protein kinase B(PI3K/AKT)in the liver of fetus.Results Transcriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver;body weight and crown-rump length were reduced(PTuKey<0.05);the level of hepatic TGs was elevated in arsenic group(PTuKey<0.05);oil-red O staining showed a significant increase in lipid droplets in arsenic group(PTuKey<0.01);the expression of lipid synthesis-related genes were significantly upregulated(PTuKey<0.05);the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated(PTuKey<0.05);the expression of PI3K,AKT decreased(PTuKey<0.05).Compared with the arsenic group,the body weight and crown-rump length of fetus increased in the arsenic+α-KG group(PTuKey<0.05);the level of hepatic TGs decreased in the arsenic+α-KG group(PTuKey<0.05);oil red O staining showed lipid droplets significantly decreased(PTuKey<0.01);the expression of lipid synthesis-related genes were downregulated(PTuKey<0.05),the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated(PTuKey<0.05);the expression levels of PI3K and AKT increased(PTuKey<0.05).Conclusion α-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through ac-tivating PI3K/AKT signaling pathway.关键词
α-酮戊二酸/砷/脂质代谢/PI3K/AKT/肝脏脂质沉积/孕期暴露/子代Key words
α-ketoglutarate/arsenic/lipid metabolism/PI3K/AKT/liver lipid deposition/gestational exposure/offspring分类
医药卫生引用本文复制引用
暴双蕊,吴红艳,孙影,詹童,杨倩,梁心茹,万志雁,陈文一,张程..α-酮戊二酸经PI3K/AKT改善砷诱导的子代肝脂质沉积[J].安徽医科大学学报,2026,61(2):225-232,8.基金项目
国家自然科学基金项目(编号:82173565) （编号:82173565）
安徽省高校中青年教师培养行动项目(编号:DTR2023012) （编号:DTR2023012）
出生人口健康教育部重点实验室"本科生开放课题"项目(编号:JKBK20249) Fund programs National Natural Science Foundation of China(No.82173565) （编号:JKBK20249）
Project for Cultivation of Young and Middle-aged Teachers in Univerisities of Anhui Province(No.DTR2023012) （No.DTR2023012）
Open Project(for Un-dergraduates)of Key Laboratory of Population Health Across Life Cycle(AHMU),MOE(No.JKBK20249) （for Un-dergraduates）
