血清胞外囊泡miR-331-5p在早发性帕金森病患者中表达水平的研究  

Serum extracellular vesicles-derived miR-331-5p in patients with early-onset Parkinson’s disease

作　　者：刘郁[1] 张静静[1] 吕荣祥[1] 王文盛[1] LIU Yu;ZHANG Jingjing;LYV Rongxiang(Department of Neurology,Ningbo Sixth Hospital,Ningbo 315000,China.)

机构地区：[1]宁波市第六医院神经内科,浙江宁波315000

出　　处：《全科医学临床与教育》2021年第6期501-505,共5页Clinical Education of General Practice

摘　　要：目的探讨早发性帕金森病(EOPD)及晚发性帕金森病(LOPD)患者血清胞外囊泡差异表达的miRNAs及潜在生物学功能。方法收集帕金森病患者18例,分为EOPD组(发病年龄≤50岁)7例及LOPD组(发病年龄>50岁)11例,收集两组患者血清并提取胞外囊泡RNA。选择11个在EOPD及LOPD患者外周血中差异表达的miRNAs,通过qRT-PCR方法检验在两组患者血清胞外囊泡中的相对水平,TargetScan数据库用于miRNA靶基因分析,String数据库用于靶基因的基因本体(GO)分析和蛋白质-蛋白质相互作用(PPI)分析,预测胞外囊泡中差异表达的miRNAs可能调控的关键靶基因及参与的生物学功能。结果与LOPD组患者相比,miR-214、miR-30b、miR-141、miR-146b-5p在EOPD患者血清胞外囊泡中表达水平下调(t分别=-7.12、-6.84、-3.61、-3.52,P均<0.05),miR-193a-3p和miR-331-5p在EOPD患者胞外囊泡中表达水平上调(t分别=23.14、25.22,P均<0.05),其中以miR-331-5p上调最为明显。GO分析发现miR-331-5p靶基因中有181个基因参与神经系统发育,在其构成的PPI网络中,节点数最高的前20个互作蛋白中MAPK1和PTEN又与神经元组成有关。结论EOPD患者血清胞外囊泡miR-331-5p表达水平上调,其可能通过靶向PTEN和MAPK1影响神经元功能,进而调节EOPD的发生发展。Objective To investigate the differentially expressed miRNAs in serum extracellular vesicles of patients with early-onset(EOPD)and late-onset(LOPD)Parkinson’s disease and potential biological function.Methods Eighteen patients with PD were collected and divided into two groups according to the age of onset:EOPD group(age≤50)with 7 cases and LODP group(age>50)with 11 cases.The patient’s serum was collected and extracellular vesicles were extracted.Eleven miRNAs with significant differences in the expression levels of EOPD and LOPD peripheral blood were selected,the levels of differentially expressed miRNAs in serum extracellular vesicles were verified by q RT-PCR.For finding key target genes regulated by extracellular vesicles miRNA,the TargetScan database was used for the analysis of miRNA target genes,and the String database was used for gene ontology(GO) and protein-protein interaction(PPI) analyses of target genes. Results Compared with the LOPD group,the miR-214,miR-30 b,miR-141,and miR-146 b-5 p in extracellular vesicles were down-regulated in patients with early-onset Parkinson’s disease(t=-7.12,-6.84,-3.61,-3.52,P<0.05),and miR-193 a-3 p and miR-331-5 p in extracellular vesicles were up-regulated in patients with early-onset Parkinson’s disease(t=23.14,25.22,P<0.05),among which extracellular vesicles derived miR-331-5 p was most significantly up-regulated.GO analysis showed that 181 target genes of miR-331-5 p participated in the development of nervous system.Among of the top 20 interacting proteins,MAPK1 and PTEN were related to formation of neurons.Conclusion The expression level of extracellular vesicles derived miR-331-5 p in serum of EOPD patients was up regulated,which may affect the function of neurons by targeting PTEN and MAPK1,and then regulate the occurrence and development of EOPD.

关 键 词：胞外囊泡 miR-331-5p 早发性帕金森病 神经元 

分 类 号：R742.5[医药卫生—神经病学与精神病学]