海南医科大学学报2025，Vol.31Issue(17)：1281-1291,11.DOI:10.13210/j.cnki.jhmu.20241016.001
益肺宣肺降浊方调控miR-485/AIM2炎症小体途径治疗血管性痴呆的机制研究
The mechanism of Yifei Xuanfei Jiangzhuo Formula in treating vascular dementia by regulating miR-485/AIM2 inflammasome pathway
摘要
Abstract
Objectives:To explore the regulatory role of miR-485/AIM2 inflammasome pathway in vascular dementia(VaD),and elucidate the mechanism of Yifei Xuanfei Jiangzhuo Formula(YFXF)in treating VaD.Methods:A VaD rat models were established by permanent ligation of bilateral common carotid arteries,which was divided into the model group,the YFXF group and the sham group.High-throughput sequencing was used to analyze the differentially expressed miRNAs.The target genes of miR-485 were predicted by TargetScan,miRDB and starBase,and validated by dual luciferase reporter gene experi-ments.Further study was conducted based on the miR-485,the rats modeled by the same method were divided into the sham group,the model group,the YFXF group,the miR-485 overexpression group,and the YFXF+miR-485 overexpression group,and the sham group.The YFXF group and the YFXF+miR-485 overexpression group were administrated with YFXF by gavage.The sham group and the model group were given equal volumes of physiological saline by gavage on a daily basis.The miR-485 overexpression group and the YFXF+miR-485 overexpression group were injected with 1.5μL of viral vector into the bilateral hip-pocampus of rats.The water maze experiment was employed to evaluate the learning and spatial memory abilities of rats,H&E staining and transmission electron microscopywere(TEM)were used to observe the morphology of hippocampal tissue.and West-ern blot was used to detect the protein expression levels of AIM2 and ASC,Caspase-1,IL-1β and IL-18.RT-PCR was used to analyze the mRNA levels of relevant genes as well as the expression levels of miR-485.Results:miR-485 exists in the common differential gene expression of 3 groups with AIM2 being its target gene.Animal experiments shows that compared with the sham group,the learning and spatial memory abilities of the model group were significantly reduced,with decreased level of miR-485 in the hippocampus tissue,and the protein levels and mRNA levels of AIM2,ASC,Caspase-1,IL-1β,and IL-18 were increased(P<0.05).Compared with the model group,the learning and memory abilities of YFXF group,miR-485 overexpression group and YFXF+miR-485 overexpression group were significantly improved,accompanied by an increase in miR-485 levels in hippocam-pal tissue,and the protein levels and mRNA levels of AIM2,ASC,Caspase-1,IL-1β,and IL-18 were decreased(P<0.05).H&E staining and TEM showed the occasional neuronal death in the sham group,severe hippocampal neuronal damage in the mod-el group,and significant improvement in neuronal damage in the other three groups compared to the model group.Among them,the improvement was most significant in the YFXF+miR-485 overexpression group.Conclusion:miR-485 can inhibit the activa-tion of AIM2 inflammasome and improve the learning and memory abilities of rats with VaD.The effect of YFXF in treating VaD is associated with regulating the miR-485/AIM2 inflammasome pathway and reducing neuronal death.关键词
益肺宣肺降浊方/血管性痴呆/miR-485/黑色素瘤缺乏因子2炎症小体Key words
Yifei Xuanfei Jiangzhuo Formula/Vascular dementia/micro RNA-485(miR-485)/AIM2 inflammasome分类
医药卫生引用本文复制引用
黄德庆,任昕怡,陈炜,卓桂锋,张金枝,苏明阳,吴林..益肺宣肺降浊方调控miR-485/AIM2炎症小体途径治疗血管性痴呆的机制研究[J].海南医科大学学报,2025,31(17):1281-1291,11.基金项目
This study was supported by the National Natural Science Foundation of China(82374387) （82374387）
Graduate Education Innovation Program of Guangxi University of Traditional Chinese Medicine(YCBXJ2023029) （YCBXJ2023029）
Guangxi University of Traditional Chinese Medicine's"Qihuang Project"High level Talent Cultivation Project(202410) 国家自然科学基金资助项目(82374387) （202410）
广西中医药大学研究生教育创新计划项目(YCBXJ2023029) （YCBXJ2023029）
广西中医药大学"岐黄工程"高层次人才培育项目(202410) （202410）
