基于lncRNA/GABAA受体探讨产后抑郁的发病及干预机制  

Study on Pathogenesis and Intervention Mechanism of Postpartum Depression Based on lncRNA/GABAA Receptors

作　　者：冀荔 王烈宏[1] 刘淑敏[2] JI Li;WANG Lie-hong;LIU Shu-min(Department of Obstetrics and Gynecology,Qinghai Red Cross Hospital,Xining 810000,China;Clinical Laboratory,Qinghai Red Cross Hospital,Xining 810000,China)

机构地区：[1]青海红十字医院妇产科,西宁810000 [2]青海红十字医院检验科,西宁810000

出　　处：《南昌大学学报（医学版）》2022年第1期1-8,共8页Journal of Nanchang University：Medical Sciences

基　　金：青海省自然科学基金(2019-q-079)。

摘　　要：目的探讨lncRNA MAGI2-AS3/miR-330/γ-氨基丁酸A(GABAA)在产后抑郁症(PPD)发病中的作用。方法建立激素模拟妊娠诱导的PPD小鼠模型,进行蔗糖偏好测试(SPT)、尾悬试验(TST)和强迫游泳测试(FST)以评估小鼠抑郁样行为。通过微阵列分析筛选出PPD小鼠海马组织中异常表达的lncRNAs/miRNAs。通过基因转染改变MAGI2-AS3和GABAA的表达,以探索它们在PPD小鼠神经元恢复中的作用以及在神经细胞中相互作用关系。通过荧光素酶测定进一步验证MAGI2-AS3/miR-330/GABAA三者间的关系。结果在行为测试中,PPD模型小鼠表现出明显的抑郁样行为。基于PPD小鼠和假手术组小鼠的海马组织进行lncRNA微阵列分析,发现在PPD小鼠中MAGI2-AS3显著上调,而miR-330显著下调(P<0.05)。RT-qPCR验证发现,PPD小鼠海马中MAGI2-AS3表达相对于假手术小鼠显著上调(P<0.05),而miR-330表达降低(P<0.05)。通过荧光素酶测定进一步验证了MAGI2-AS3和miR-330之间的结合关系,并确定了GABAA作为miR-330的下游分子。功能实验分析显示,上调PC12细胞中MAGI2-AS3表达导致GABAA表达增加(P<0.05),但转染miR-330模拟物使细胞中GABAA表达降低(P<0.05)。向PPD小鼠海马中注射sh-MAGI2-AS3或sh-GABAA后,海马组织中神经元损伤减少(P<0.05)。结论MAGI2-AS3通过miR-330/GABAA网络参与神经元损伤并增加PPD模型中的神经元丢失。Objective To explore the role of lncRNA MAGI2-AS3/miR-330/γ-aminobutyric acid A(GABAA)in the pathogenesis of postpartum depression(PPD).Methods A mouse model of hormone-simulating pregnancy-induced PPD was established.Sucrose preference test(SPT),tail suspension test(TST)and forced swimming test(FST)were performed to evaluate the depression-like behaviors in mice.The abnormally expressed lncRNAs/miRNAs in PPD mice were screened by microarray analysis.The expression of MAGI2-AS3 and GABAA was altered by gene transfection to explore their roles in neuronal recovery and their interaction in neuronal cells.The relationships among MAGI2-AS3,miR-330 and GABAA were verified by luciferase assay.ResultsIn the behavior test,PPD mice showed obvious depression-like behaviors.The lncRNA microarray analysis based on the hippocampal tissues of PPD mice and sham-operation mice showed that MAGI2-AS3 expression was up-regulated but miR-330 expression was down-regulated in PPD mice(P<0.05).The results were further verified by RT-qPCR(P<0.05).The binding relationship between MAGI2-AS3 and miR-330 was proved by luciferase assay,and GABAA was confirmed as a downstream molecule of miR-330.Functional experimental analysis showed that overexpression of MAGI2-AS3 led to an increase in GABAA expression in PC12 cells(P<0.05).However,GABAA expression was decreased in cells transfected with miR-330 mimic(P<0.05).After injection of sh-MAGI2-AS3 or sh-GABAA,neuronal injury was reduced in the hippocampus of PPD mice(P<0.05).Conclusion MAGI2-AS3 participates in neuronal damage and increases neuronal loss in PPD mice through the miR-330/GABAA network.

关 键 词：lncRNA MAGI2-AS3 miR-330 γ-氨基丁酸A 产后抑郁症 动物 实验 小鼠 

分 类 号：R-332[医药卫生] R749