摘要
目的探究微小RNA-146a(miR-146a)对阿尔茨海默病(AD)大鼠认知能力、辅助性T细胞(Th17)/调节性T细胞(Treg)分布及炎症因子水平的影响。方法SD大鼠60只,随机分为假手术组、AD组和miR-146a+AD组各20只。AD组、miR-146a+AD组于海马组织注射Aβ25-35制作AD模型,假手术组仅开颅窗后注射等量生理盐水,用骨蜡封闭。miR-146a+AD组随即通过尾静脉注射1×108 PFU/mL的miR-146a agomir 100μL。采用水迷宫实验评价大鼠认知能力,流式细胞术检测血清Th17/Treg分布,ELISA法检测海马组织中的肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-1β、IL-6。结果AD组造模1~4 d逃逸潜伏期均长于假手术组,目标象限停留时间与穿越平台次数少于假手术组;miR-146a+AD组逃逸潜伏期短于AD组,目标象限停留时间与穿越平台次数高于AD组(P均<0.05)。AD组CD4+IL-17A+Th17比例低于假手术组、CD4+CD25+Foxp3+Treg比例高于假手术组;miR-146a+AD组CD4+IL-17A+Th17比例高于AD组、CD4+CD25+Foxp3+Treg比例低于AD组(P均<0.05)。AD组血清IL-1β、IL-6、TNF-α水平高于假手术组,miR-146a+AD组血清IL-1β、IL-6、TNF-α水平低于AD组(P均<0.05)。结论miR-146a尾静脉注射可改善AD大鼠的认知能力,调节Th17/Treg平衡,减轻AD脑部炎症。
Objective To investigate the effects of microRNA-146a(miR-146a)on cognitive ability,Th17/Treg distribution and inflammatory factor levels in Alzheimer's disease(AD)rats.Methods Sixty SD rats were randomly di-vided into the sham operation group,AD group and miR-146a+AD group,with 20 cases in each group.Rats in the AD group and miR-146a+AD group were injected with Aβ25-35 in the hippocampus to make AD models,while the rats in the sham operation group were only injected with the same amount of normal saline after craniotomy,and sealed with bone wax.The rats in the miR-146a+AD group were then injected with 100μL of 1×108 PFU/mL of miR-146a agomir through the tail vein.Cognitive ability of rats was evaluated by water maze test,serum Th17/Treg distribution was detected by flow cytometry,and inflammatory factors tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in hippocampus were detected by ELISA.Results The escape latency from 1 to 4 days after modeling in the AD group was longer than that in the sham operation group,the duration of stay in the target quadrant was shorter and the number of crossing the plat-form was smaller than those in the sham operation group,and the escape latency in the miR-146a+AD group was shorter than that in the AD group,and the duration of stay in the target quadrant was longer and the number of crossing the plat-form was larger than those in the AD group(all P<0.05).The ratio of CD4+IL-17A+Th17 was lower,and the ratio of CD4+CD25+Foxp3+Treg was higher in the AD group than those in the sham operation group;the ratio of CD4+IL-17A+Th17 was higher,and the ratio of CD4+CD25+Foxp3+Treg was lower in the miR-146a+AD group than those of the AD group(all P<0.05).The levels of serum IL-1β,IL-6,and TNF-αin the AD group were higher than those in the sham operation group,and the levels of serum IL-1β,IL-6,and TNF-αin the miR-146a+AD group were lower than those in the AD group(all P<0.05).Conclusion MiR-146a can improve the cognitive ability of AD rats,regulate Th17/Treg balance,and r
作者
谢平安
廖辉
张艳敏
杜从斌
XIE Ping'an;LIAO Hui;ZHANG Yanmin;DU Congbin(Department of Geriatrics,The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300192,China;不详)
出处
《山东医药》
CAS
2022年第20期46-49,共4页
Shandong Medical Journal
基金
天津市卫生健康科技项目(ZC20230)。
