摘要
目的探讨氟中毒诱导重度抑郁症相关基因的潜在作用机制及原花青素(proanthocyanidin,PC)的缓解作用。方法从基因表达综合数据库获取暴露于氟的神经胶质细胞数据集和抑郁症患者的基因数据。分析其差异表达基因(differential expressed gene,DEG),通过基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析及蛋白质–蛋白质相互作用(protein-protein interaction,PPI)分析筛选关键基因,并构建关键基因–微RNA(microRNA,miRNA)与关键基因–转录因子(transcription factor,TF)网络,随后进行配体与关键靶点的分子对接。采用蛋白质印迹法检测SH-SY5Y细胞中多腺苷二磷酸核糖聚合酶(poly adenosine diphosphate-ribose polymerase,PARP)1、cleaved-PARP表达情况。结果筛选得到95个共同DEG,主要富集在细胞凋亡等通路中。筛选出3个关键基因(UQCRQ、SNRPD2和TIMM10),受试者操作特征曲线分析显示TIMM10对抑郁症的预测能力最强;关键基因-miRNA网络得出5个miRNA共同调控这3个关键基因;关键基因-TF网络得出ELF1调控这3个关键基因。分子对接表明UQCRQ受体与PC配体具有较高的亲和力。体外实验结果显示,Na F组的PARP1表达低于对照组(P<0.05),NaF+PC组的PARP1表达高于NaF组(P<0.05)。Na F组的cleaved-PARP表达显著高于对照组(P<0.05),NaF+PC组的cleaved-PARP表达显著低于NaF组(P<0.05)。结论PC可有效减轻氟中毒引起的重度抑郁症,且对其有一定保护作用。
Objective To explore the potential mechanism of action of genes related to severe depression induced by fluoride and the alleviating effect of proanthocyanidin(PC).Methods The datasets of glial cells exposed to fluoride and the genetic data of patients with depression were obtained from the Gene Expression Omnibus.Analyze the differential expressed genes(DEG),and screen out the key genes through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and protein-protein interaction(PPI)analysis.And construct the key gene-microRNA(miRNA)and key gene-transcription factor(TF)networks,and then carry out molecular docking of ligands with key targets.The expression of poly adenosine diphosphate-ribose polymerase(PARP)1 and cleaved-PARP in SH-SY5Y cells was detected by Western blotting.Results A total of 95 common DEGs were screened out,mainly enriched in pathways such as apoptosis.Three key genes(UQCRQ,SNRPD2 and TIMM10)were screened out.Receiver operating characteristic curve analysis showed that TIMM10 had the strongest predictive ability for depression.The key gene-miRNA network indicated that five miRNAs jointly regulate these three key genes.The key gene-TF network concluded that ELF1 regulated these three key genes.Molecular docking indicated that the UQCRQ receptor had a high affinity for the PC ligand.The results of in vitro experiments showed that the expression of PARP1 in NaF group was lower than that in control group(P<0.05),while the expression of PARP1 in NaF+PC group was higher than that in NaF group(P<0.05).The expression of cleaved-PARP in NaF group was significantly higher than that in control group(P<0.05),and the expression of cleaved-PARP in NaF+PC group was significantly lower than that in NaF group(P<0.05).Conclusion PC can effectively alleviate severe depression caused by fluoride and has a certain protective effect on depression.
作者
肖梦欢
吴志宇
颜楚麟
牛强
马娇龙
郭淑霞
XIAO Menghuan;WU Zhiyu;YAN Chulin;NIU Qiang;MA Jiaolong;GUO Shuxia(Department of Preventive Medicine,School of Medicine,Shihezi University,Key Laboratory of the Corps for Prevention and Control of Important Emerging Infectious Diseases and Public Health Security,Shihezi 832003,Xinjiang,China)
出处
《中国现代医生》
2025年第34期1-7,共7页
China Modern Doctor
基金
国家自然科学基金项目(82360671,82060580)。
