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基于“陈气致病”理论研究miRNA-mRNA网络调控糖尿病动脉粥样硬化的机制

Research on the mechanism of miRNA-mRNA network regulation of diabetic atherosclerosis based on the theory of"Chen Qi"
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摘要 目的探讨糖尿病动脉粥样硬化关键基因及“陈气致病”科学内涵。方法糖尿病动脉粥样硬化模型小鼠与白血病病毒B株敏感(Friend Virus B NIH Jackson,FVB)小鼠各9只,采用GO和KEGG分析差异基因分子功能、生物过程、细胞成分及通路富集情况,采用免疫组化检测核苷酸结合寡聚化结构域样受体含pyrin结域蛋白3(NLR family pyrin domain containing 3,NLRP3)在海马、胃、心肌及主动脉组织中表达,构建miRNA-mRNA网络,采用实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)验证该网络。结果46个DEGs在模型小鼠主动脉组织中差异表达。GO表明DEGs生物过程主要集中于miRNA介导的翻译抑制、皮脂腺发育等方面,分子功能主要集中于内涵体、内体膜等方面,细胞成分主要集中于通道活性、磷脂酰肌醇-3-磷酸结合等方面。KEGG表明DEGs富集于白细胞经内皮细胞迁移过程、叉头转录因子(forkhead box class O,FoxO)信号通路等方面;免疫组化结果提示在主动脉组织中NLRP3含量最高;构建由46个mRNA及23个miRNA组成miRNA-mRNA调控网络,Miranda分析提示小鼠主动脉中miR-874-3p与NLRP3的3’端非编码区(non-coding region,UTR)存在互补结合位点,qPCR结果表明,模型小鼠主动脉组织中NLRP3水平显著升高,miR-874-3p水平显著降低。结论高糖环境中低表达的miR-874-3p对NLRP3的抑制减弱可能是糖尿病动脉粥样硬化炎症形成的重要机制及“陈气致病”的科学内涵。 Objective To investigate the key genes of diabetic atherosclerosis and the scientific connotation of"stale gas causing disease".Methods Nine mice of diabetic atherosclerosis model and nine mice of Friend Virus B NIH Jackson(FVB)were analyzed by GO and KEGG for the molecular function,biological process,cellular composition and pathway enrichment of different genes,and immunohistochemistry for the detection of NLR family pyrin domain containing 3(NLRP3)in the hippocampus,stomach,myocardium,and the heart muscle.The expression of NLR family pyrin domain containing 3(NLRP3)in hippocampus,stomach,myocardium and aorta was detected by immunohistochemistry.miRNA-mRNA network was constructed and validated by qPCR.Results 46 DEGs were differentially expressed in the aortic tissues of model mice.GO indicated that the biological processes of DEGs were mainly focused on miRNA-mediated translational repression and the development of sebaceous glands,the molecular functions of DEGs were mainly focused on endosomes and endosomal membranes,and the cellular components of DEGs were mainly focused on the channel activity and the binding of phosphatidylinositol-3-phosphate.KEGG showed that DEGs were enriched in leukocyte transendothelial cell migration and forkhead box class O(FoxO)signaling pathway,etc.Immunohistochemistry showed that NLRP3 content was the highest in aortic tissues,and a miRNA-mRNA regulatory network was constructed,consisting of 46 mRNAs and 23 miRNAs.Miranda analysis suggested that there was a complementary binding site between miR-874-3p and the non-coding region(UTR)at the 3'end of NLRP3 in the aorta of mice.qPCR results showed that the level of NLRP3 in the aortic tissues of the model mice was significantly elevated,and the level of miR-874-3p was significantly reduced.The qPCR results showed that NLRP3 levels were significantly increased and miR-874-3p levels were significantly decreased in the aortic tissues of model mice.Conclusion The weakening of NLRP3 inhibition by miR-874-3p in high glucose environment may be an important mechanism of diabetic atherosclerotic inflammation and the scientific connotation of"Chenqi causes disease".
作者 王瑾茜 雷唯一 喻嵘 杜珊 雷诗卉 张田田 刘洋洋 李薇 杨蕙 陈亚 余文运 黄娟 WANG Jin-xi;LEI Wei-yi;YU Rong;DU Shan;LEI Shi-hui;ZHANG Tian-tian;LIU Yang-yang;LI Wei;YANG Hui;CHEN Ya;YU Wen-yun;HUANG Juan(First Hospital of Hunan University of Chinese Medicine,Changsha,Hunan 410007,China;Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;Hunan Province Academy of Chinese Medicine,Chang-sha,Hunan 410031,China;Beitang Street Community Health Service Center,Binhai New Area,Tianjin 300453,China)
出处 《时珍国医国药》 CAS CSCD 北大核心 2024年第12期2883-2890,共8页 Lishizhen Medicine and Materia Medica Research
基金 国家自然科学基金区域联合创新研究重点支持项目(U21A20411) 湖南省自然科学基金青年项目(2023JJ40505) 湖南省自然科学基金医卫行业联合基金(2024JJYWLH0500) 湖南省卫健委科研基金(w20243161) 湖南中医药大学校级科研基金(2022XYLH005)。
关键词 MIRNA MRNA 糖尿病动脉粥样硬化 虚瘀毒 陈气致病 miRNA mRNA Diabetic atherosclerosis Blood stasis toxin Pathogenesis of"Chenqi"
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