miR-92b-3p抑制物在阿尔兹海默病并发癫痫动物模型中的抗癫痫效应  

Antiepileptic Effects of Inhibitors of MiR-92b-3p in Animal Models of Alzheimer's Disease Complicated by Epilepsy

作　　者：陶华 吴郑娟 张小璐 刘杨 周煦 TAO Hua;WU Zhengjuan;ZHANG Xiaolu;LIU Yang;ZHOU Xu(Affiliated Hospital of Guangdong Medical University,Guangdong Zhanjiang 524001;Clinical Research and Experimental Center,Affiliated Hospital of Guangdong Medical University,Guangdong Zhanjiang 524001)

机构地区：[1]广东医科大学附属医院,广东湛江524001 [2]广东医科大学附属医院临床研究实验中心,广东湛江524001

出　　处：《深圳中西医结合杂志》2024年第11期4-7,I0002,I0003,共6页Shenzhen Journal of Integrated Traditional Chinese and Western Medicine

基　　金：湛江市科技计划项目(2021A05051)。

摘　　要：目的:评估miR-92b-3p抑制物在阿尔兹海默病(AD)并发癫痫动物模型中的抗癫痫效应。方法:通过生物信息学方法和双荧光素酶实验筛选解整合素金属蛋白酶10(ADAM10)的调控分子,采用实时定量聚合酶链反应和Western Blot评估miR-92b-3p和ADAM10在神经元细胞和AD并发癫痫动物模型中的表达水平,经鼻腔给药方法给予miR-92b-3p的抑制物,评估其在AD并发癫痫动物模型中的抗癫痫效应。结果:通过生物信息学方法,双荧光素酶实验,Western Blot条带及其灰度分析,确认miR-92b-3p可转录后调控ADAM10,且在神经元细胞中对ADAM10调控作用较强。与AD动物模型组相比,miR-92b-3p在AD并发癫痫动物模型(AD+EP)组中显著上调。与AD+EP组相比,经鼻腔给予miR-92b-3p抑制物的治疗组癫痫发生率,Racine 4级以上发生率均显著减少。Racine 4级以上发作的潜伏期显著延长。结论:本研究初步证实miR-92b-3p抑制物在AD并发癫痫动物模型中具有抗癫痫效应。Objective To evaluate the antiepileptic effect of miR-92b-3p inhibitor in Alzheimer's disease(AD)animal model with epilepsy.Methods Regulatory molecules of a disintegrin and metalloprotease 10(ADAM10)were screened using bioinformatics methods and dual-luciferase assays.The expression levels of miR-92b-3p and ADAM10 in neuronal cells and animal models of AD with epilepsy were evaluated using real-time quantitative polymerase chain reaction and Western blot.Finally,miR-92b-3p inhibitors were administered via nasal administration to assess their antiepileptic effects in AD induced epilepsy animal models.Results By bioinformatics methods,dual-luciferase assay,Western blot bands and grayscale analysis,it was confirmed that miR-92b-3p could post-transcriptionally regulate ADAM10,and had a strong regulatory effect on ADAM10 in neuronal cells.MiR-92b-3p was significantly upregulated in AD complicated epilepsy animal model(AD+EP)group compared with AD animal model group.Compared with AD+EP group,the incidence of epilepsy,the incidence of Racine grade 4 or higher were significantly reduced,and the latency of Racine grade 4 or higher seizures was significantly prolonged in the treatment group given miR-92b-3p inhibitor intranasally.Conclusion In this study,we preliminarily confirmed that the inhibitor of miR-92b-3p has an antiepileptic effect in an animal model of AD complicated with epilepsy.

关 键 词：阿尔兹海默病 癫痫 MIRNAS miR-92b-3p 抑制物 

分 类 号：R725[医药卫生—儿科]