miR-143-3p和BCL2在早发性帕金森病患者血清胞外囊泡中异常表达  

Abnormal expressions of micro RNA-143-3p and B-cell lymphoma-2 in serum extracellular vesicles of 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;Lyu Rongxiang;Wang Wensheng(Department of Neurology,Ningbo Sixth Hospital,Ningbo 315040,China)

机构地区：[1]宁波市第六医院神经内科,315040

出　　处：《中华神经医学杂志》2019年第1期17-21,共5页Chinese Journal of Neuromedicine

摘　　要：目的 明确帕金森病(PD)患者及健康个体血清胞外囊泡(EVs)中差异表达的miRNAs及影响PD进展的可能机制。 方法 收集自2015年1月至2017年11月于宁波市第六医院神经内科确诊的早发性PD(EOPD)患者(起病年龄≤50岁)20例,晚发性PD(LOPD)患者(起病年龄>50岁)36例,以及门诊体检健康对照个体10例,分别定义为EOPD组、LOPD组和对照组。采集3组受试者血清并提取EVs,采用miRNA表达谱芯片及实时荧光定量PCR(qRT-PCR)分析并验证PD患者和健康个体血清EVs间差异表达的miRNAs。采用Cytoscape分析差异表达miRNAs间共同调控的靶基因,采用String数据库分析靶基因间相互作用及其功能。检测并分析差异表达miRNAs及靶基因在EOPD及LOPD患者中的相对表达水平及相关性。 结果 与对照组成员相比,LOPD患者血清EVs中miR-143-3p和miR-1180表达水平上调,miR-451和miR-500a-5p表达水平下调,差异有统计学意义(P<0.05)。miR-143-3p在EOPD患者中表达水平显著高于LOPD患者,差异有统计学意义(t=3.888,P=0.018)。miRNAs靶基因及其蛋白质-蛋白质相互作用分析结果显示,B淋巴细胞瘤-2(BCL2)和AKT1是miR-143-3p的关键靶基因。EOPD患者EVs中BCL2表达水平显著高于LOPD患者及对照组成员,差异有统计学意义(P<0.05);EOPD患者血清EVs中BCL2和miR-143-3p表达水平呈负相关关系(r=-0.556,P=0.025)。 结论 miR-143-3p与靶基因BCL2在EOPD患者血清EVs中表达水平呈负相关关系,其表达水平变化可能与突触结构可塑性和神经细胞凋亡有关。Objective To explore the differentially expressed micro RNAs (miRNAs) in serum-derived extracellular vesicles (EVs) of patients with Parkinson's disease (PD) and healthy individuals. Methods Thirty-six patients with late-onset Parkinson's disease (LOPD, age of onset being more than 50 years), 20 patients with early-onset Parkinson's disease (EOPD, age of onset being no more than 50 years), and 10 healthy individuals were collected in our hospital from January 2015 to December 2017. Serum of all subjects was collected and EVs were extracted. The miRNA chip and real-time quantitative (qRT)-PCR were used to analyze and verify the differentially expressed exosomal miRNAs between PD patients and healthy individuals;Cytoscape software was used to analyze the common target genes regulated by differentially expressed miRNAs, and String database was used to analyze the interaction and function of target genes. And qRT-PCR was further used to analyze the expression level and correlation of differentially expressed miRNAs and their target genes in patients with EOPD and LOPD, respectively. Results As compared with healthy individuals, LOPD patients had significantly up-regulated expression levels of miR-143-3p and miR-1180 in the serum derived EVs, and statistically down-regulated miR-451 and miR-500 levels (P<0.05). The miR-143-3p expression level in EOPD patients was significantly higher than that in LOPD patients (t=3.888, P=0.018). The target genes B-cell lymphoma-2 (BCL2) and AKT1 were involved in regulating the cholinergic synapses and neurotrophin signaling pathways, and the BCL2 relative expression level in EOPD patients was significantly higher than that in LOPD patients and healthy controls (P<0.05);and the relative expression levels of BCL2 and miR-143-3p were negatively correlated in the serum derived EVs of EOPD patients (r=-0.556, P=0.025). Conclusion The miR-143-3p and BCL2 expression levels are negatively correlated in the serum derived EVs of EOPD patients;changes of expression level may be related to plast

关 键 词：早发性帕金森病 胞外囊泡 miR-143-3p B淋巴细胞瘤-2 

分 类 号：R742.5[医药卫生—神经病学与精神病学]