中国中医急症2025，Vol.34Issue(5)：772-777,6.DOI:10.3969/j.issn.1004-745X.2025.05.005
基于外泌体miRNA高通量测序探讨桃红四物汤对深静脉血栓模型大鼠血栓形成的影响
Exploring the Effect of Taohong Siwu Decoction on Thrombosis in a Rat Model of Deep Vein Thrombosis Based on Exosomal miRNA High-Throughput Sequencing
摘要
Abstract
Objective:To investigate the effect of Taohong Siwu Decoction on thrombosis in a rat model of deep vein thrombosis(DVT)based on exosomal microRNA(miRNA)high-throughput sequencing.Methods:Rats were pre-treated with different doses of Taohong Siwu Decoction(4,8,16 g/kg)via gavage for 7 days before model es-tablishment.The model group was given an equal volume of distilled water by gavage.DVT was induced by ligat-ing the inferior vena cava below the left renal vein and all side branches,and clamping the junction of the iliac vein for 15 minutes.Thrombi were extracted from each group to measure their weight and length.Pathological changes were observed using hematoxylin-eosin(HE)staining.Plasma exosomes(Exos)were isolated,and their morphology was observed under transmission electron microscopy.Nanoparticle tracking analysis was used to deter-mine their size distribution and concentration.High-throughput sequencing was performed to screen significantly differentially expressed miRNAs in Exos between the model group and the optimal dose treatment group.Target gene prediction,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analy-ses were conducted.Results:Exos in all groups exhibited a"cup-shaped"bilayer membrane structure,with most Exos having a diameter of approximately 84 nm.Compared with the model group,the thrombus length and weight were significantly reduced in the Taohong Siwu Decoction-L,Taohong Siwu Decoction-M,and Taohong Siwu De-coction-H groups(P＜0.05 or P＜0.01).HE staining of the inferior vena cava showed a decreasing trend in inflam-matory cell infiltration and thromboembolism severity in the Taohong Siwu Decoction treatment groups,with the Taohong Siwu Decoction-H group showing the best recovery.High-throughput sequencing and bioinformatics anal-ysis revealed 54 differentially expressed miRNAs between the model group and the Taohong Siwu Decoction-H group,including 3 upregulated and 51 downregulated miRNAs,corresponding to 1 393 differentially expressed mRNAs.GO analysis indicated functions related to dephosphorylation,synaptic membranes,and metal ion trans-membrane transporter activity.KEGG pathway analysis showed that differentially expressed genes were mainly en-riched in pathways such as MAPK,Ras,Rap-1,cAMP,mTOR,and sphingolipid signaling.Conclusion:Taohong Siwu Decoction-H group has the optimal dose for preventing and treating DVT in rats.Bioinformatics analysis of sequencing results suggests that the MAPK,Ras,Rap-1,cAMP,and mTOR signaling pathways may be key path-ways through which Taohong Siwu Decoction prevents and treats DVT.关键词
下肢深静脉血栓/桃红四物汤/外泌体/miRNA/大鼠Key words
Low limbs deep vein thrombosis/Taohong Siwu Decoction/Exosomes/miRNA/Rats分类
医药卫生引用本文复制引用
蒋雄一郎,林少如,匡慧芳,贺玉楼,蔡哲夫,董克芳,曾祥晶..基于外泌体miRNA高通量测序探讨桃红四物汤对深静脉血栓模型大鼠血栓形成的影响[J].中国中医急症,2025,34(5):772-777,6.基金项目
湖南省教育厅优秀青年项目(22B0353) （22B0353）
湖南省中医药管理局科研课题(C2023022) （C2023022）
湖南中医药大学校级科研项目(2022XYLH036) （2022XYLH036）
湖南省中医药管理局田心义名医工作室项目(国中医药办人教函[2021]270号) （国中医药办人教函[2021]270号）
