首页|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

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

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

Alzheimer's diseaseEpilepsyMiRNAsMiR-92b-3pInhibitors

陶华、吴郑娟、张小璐、刘杨、周煦

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广东医科大学附属医院,广东 湛江 524001

广东医科大学附属医院临床研究实验中心,广东 湛江 524001

阿尔兹海默病 癫痫 miRNAs miR-92b-3p 抑制物

湛江市科技计划项目

2021A05051

2024

深圳中西医结合杂志
深圳市中西医结合临床研究所

深圳中西医结合杂志

影响因子:0.692
ISSN:1007-0893
年,卷(期):2024.34(11)