基础医学与临床2026，Vol.46Issue(3)：339-344,6.DOI:10.16352/j.issn.1001-6325.2026.03.0339
Nlrp3T346M突变转基因小鼠呈现昼夜节律同步化异常并影响肝脏炎性损伤
Nlrp3T346M mutant transgenic mice present abnormal circadian entrainment and affect liver inflammatory injury
摘要
Abstract
Objective To explore the potential mechanism by which NLRP3 mutation leads to its sustained activa-tion and subsequent liver injury at the transcriptome level with an animal model of Nlrp3T346M mutant transgenic mice.Methods Liver tissues from Nlrp3T346M mice and their wild type(WT)littermates were subjected to tran-scriptome sequencing.Gene expression difference between the two groups was analyzed,followed by GO and KEGG enrichment analyses of the differentially expressed genes(DEGs).RT-qPCR was performed to verify the expression of relevant DEGs.Results Compared with WT group,a total of 258 DEGs were screened in the livers of Nlrp3T346M mice,of which 197 were up-regulated and 61 were down-regulated.Enrichment analysis showed that the DEGs were mainly involved in circadian entrainment,as well as metabolic pathways of steroids,retinol and olefinic compounds,etc.RT-qPCR results showed mRNA expression trends of key DEGs in the circadian entrainment pathway,namely Cacna1h,Camk2b,Gnai1,Mtnr1a and Nos1ap were consistent with those observed in the tran-scriptome sequencing.Conclusions Sustained activation of NLRP3 in the liver tissue of Nlrp3T346M mice may inter-fere with circadian entrainment,which in turn disrupts temporal regulation of downstream metabolism and hormone secretion,thus leads to liver injury.关键词
Nlrp3突变/转基因小鼠/肝脏/转录组测序(RNA-seq)/昼夜节律同步化Key words
Nlrp3 mutation/transgenic mouse/liver/RNA sequencing(RNA-seq)/circadian entrainment分类
医药卫生引用本文复制引用
王雨鑫,杨梅,陈泉霖,朱蕾..Nlrp3T346M突变转基因小鼠呈现昼夜节律同步化异常并影响肝脏炎性损伤[J].基础医学与临床,2026,46(3):339-344,6.基金项目
中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-005,2025-I2M-KJ-009) （2021-I2M-1-005,2025-I2M-KJ-009）
中央高水平医院临床科研业务费(2022-PUMCH-C-025) （2022-PUMCH-C-025）
