昆明医科大学学报2025，Vol.46Issue(12)：21-29,9.DOI:10.12259/j.issn.2095-610X.S20251203
抑制lncRNA H19表达对血管性痴呆模型神经炎症及认知功能的影响
Effects of Inhibiting lncRNA H19 Expression on Neuroinflammation and Cognitive Function in Vascular Dementia Models
摘要
Abstract
Objective To explore the effects of long non-coding RNA(lncRNA)H19 on neuroin-flammation and cognitive function in a vascular dementia(VD)model.Methods A VD mouse model was established by bilateral common carotid artery occlusion.Forty-eight mice were randomly and equally divided into four groups:sham surgery group,model group,NC group,and shRNA-H19 group.The sham surgery group underwent no ligation.Following successful model establishment,AAV2/1-shRNA-vehicle and AAV2/1-shRNA-H19 were injected into the brain of mice in the NC group and shRNA-H19 group,respectively.Cognitive levels was assessed useing Morris water maze test.Pathological changes in the hippocampal CA1 region and neuronal injury w ere observed by HE and Nissl staining.Neuronal apoptosis was detected by TUNEL staining.Levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in hippocampal tissue were measured by enzyme-linked immunosorbent assay(ELISA).Expression of ionized calcium-binding adapter molecule-1(Iba-1)protein in the hippocampal CA1 region was detected by immunofluorescence staining.Expression of H19,B-cell lymphoma-2(Bcl-2),cleaved caspase-3,toll-like receptor 4(TLR4),and nuclear factor-kappa B(NF-κB)protein and/or mRNA in hippocampal tissue were detected by quantitative real-time polymerase chain reaction(qRT-PCR)and/or Western blot.Results Compared with the model group,shRNA-H19 mice exhibited improved cognitive function(P<0.05),reduced pathological changes and neuronal injury in the hippocampal CA1 region,elevated Bcl-2 levels in hippocampal tissue,and decreased neuronal apoptosis rate,H19,TNF-α,IL-1β,IL-6,Iba-1,cleaved caspase-3,TLR4,and NF-κB p-p65/NF-κB p65 levels(P<0.05).The NC group showed no significant differences in the above indicators(P>0.05).Conclusion Inhibition of H19 expression in hippocampal tissue ameliorates neuroinflammation and improve cognitive function in VD mice,inhibits neuronal apoptosis and microglial infiltration in the hippocampal CA1 region.The underlying mechanism may be related to downregulation of the TLR4/NF-κB p65 signaling pathway.关键词
血管性痴呆/长非编码RNA H19/神经元凋亡/神经炎症/TLR4/NF-κB p65通路/小鼠Key words
Vascular dementia/Long non-coding RNA H19/Neuronal apoptosis/Neuroinflammation/TLR4/NF-ΚB P65 pathway/Mice分类
医药卫生引用本文复制引用
BAI Haixiao,WANG Huan,DUAN Xinfei,FANG Pingping,LI Xiao,JIA Jundong..抑制lncRNA H19表达对血管性痴呆模型神经炎症及认知功能的影响[J].昆明医科大学学报,2025,46(12):21-29,9.基金项目
河北省卫生健康委员会医学科学研究计划项目(20242344) （20242344）
