实用医学杂志2024,Vol.40Issue(4):453-459,7.DOI:10.3969/j.issn.1006-5725.2024.04.003
miR-421靶向调控Menin/Caspase-3影响抑郁症的机制
The mechanism of target regulating of miR-421 to Menin/Caspase-3 pathway for depression
摘要
Abstract
Objective To explore the mechanism of miR-421 affecting the occurrence and development of depression.Methods A depressive rat model was established by single intraperitoneal injection of lipopolysaccharide(LPS),and depressive behavior was detected by glucose preference test and open-field test.miRNA microarray chips and RT-PCR were used to analyze the expression level of miR-421 in hippocampus of the depressed rats.TargetScan database and mi RDB database were used to predict the target genes of miR-421.Dual luciferase reporter gene assay was used to observe the binding of miR-421 to the target genes.The impact of over-expression and inhibition of miR-421 on target genes was observed,then the influence of over-expression and inhibition of target genes on downstream factors was observed,and the related mechanism of miR-421 on depression was explored.Results miRNA microarray chips and RT-PCR assay showed that miR-421 was highly expressed in the hippocampus of the depressed rats(P<0.001),Inhibition of miR-421 expression could significantly restore the body weight and exercise ability of the depressed rats(P<0.001).Binding targets of Menin and miR-421 were predicted by TargetScan database,and interaction between Menin and miR-421 was demonstrated by dual-luciferase reporter gene assay.Menin expression was down-regulated while miR-421 was overexpressed(P<0.001),whereas it was up-regulated as miR-421 was inhibited(P<0.001).qPCR indicated that expressions of Caspase-3 and NF-κB in the hippocampus of the depressed rats was significantly increased(P<0.001),and IL-1β expression in the hippo-campus was significantly increased(P<0.01).When the expression of Menin was inhibited,the expressions of Caspase-3,NF-κB and IL-1β were increased(P<0.001),while the expressions of Caspase-3,NF-κB and IL-1β were decreased when Menin was overexpressed(P<0.001).Conclusions Inhibition of miR-421 expression can increase Menin expression,decrease Caspase-3 content,and reduce neuroinflammatory response,thereby improving depressive symptoms.关键词
抑郁症/miR-421/Menin/Caspase-3/动物实验/作用机制Key words
depression/miR-421/menin/caspase 3/animal experiments/mechanism分类
医药卫生引用本文复制引用
刘永辉,谭庆晶,陈清,韦理萍,杨俊威,杨侃,高玉广..miR-421靶向调控Menin/Caspase-3影响抑郁症的机制[J].实用医学杂志,2024,40(4):453-459,7.基金项目
广西自然科学基金面上项目(编号:2020GXNSFAA297161) (编号:2020GXNSFAA297161)
第七批全国老中医专家学术经验继承工作(编号:国中医药人教函[2022]76号) (编号:国中医药人教函[2022]76号)
广西中医临床优秀人才项目(编号:桂中医药科教发[2022]14号) (编号:桂中医药科教发[2022]14号)
刘泰广西名中医传承工作室建设项目(编号:桂中医药科教发[2021]6号) (编号:桂中医药科教发[2021]6号)