中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (25): 6455-6462.doi: 10.12307/2026.475

• 骨组织构建 bone tissue construction • 上一篇    下一篇

胫骨横向骨搬移治疗兔糖尿病足溃疡模型的转录组测序分析

李豪杰1，谢同亮1，李  瑞1，孙祖延1，邓  江1，徐  林1，黄文良2   

  1. 1遵义医科大学第三附属医院，贵州省遵义市   563000；2贵州省茅台医院，贵州省仁怀市   564500
  • 收稿日期:2025-10-15 修回日期:2026-03-09 出版日期:2026-09-08 发布日期:2026-04-17
  • 通讯作者: 黄文良，在读博士，硕士研究生导师，主任医师，贵州省茅台医院骨科，贵州省仁怀市 564500
  • 作者简介:李豪杰，男，1998年生，贵州省遵义市人，汉族，遵义医科大学骨科在读硕士研究生，主要从事骨科疾病研究。
  • 基金资助:
    贵州省科技计划项目(黔科合基础-ZK[2021]一般387)，项目负责人：黄文良；贵州省临床专项项目(黔科合成果-LC[2024]019)，项目负责人：黄文良；贵州茅台医院项目(MTyk2025-37)，项目负责人：黄文良

Transcriptome sequencing analysis of tibial transverse transport in a rabbit model of diabetic foot ulcers

Li Haojie1, Xie Tongliang1, Li Rui1, Sun Zuyan1, Deng Jiang1, Xu Lin1, Huang Wenliang2   

  1. 1The Third Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China; 2Kweichow Moutai Hospital, Renhuai 564500, Guizhou Province, China
  • Received:2025-10-15 Revised:2026-03-09 Online:2026-09-08 Published:2026-04-17
  • Contact: Huang Wenliang, PhD candidate, Master’s supervisor, Chief physician, Kweichow Moutai Hospital, Renhuai 564500, Guizhou Province, China
  • About author:Li Haojie, MS candidate, The Third Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
  • Supported by:
    Guizhou Provincial Science and Technology Program Project, No. ZK[2021]General 387 (to HWL); Guizhou Provincial Clinical Special Project, No. LC[2024]019 (to HWL); Kweichow Moutai Hospital Project, No. MTyk2025-37 (to HWL) 

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摘要：



文题释义：
胫骨横向骨搬移术：治疗原理是通过持续、稳定的机械牵拉，调节手术区域及周围组织的微循环，进而改善细胞代谢并加速组织再生和修复。目前，胫骨横向骨搬移术已成为治疗糖尿病足溃疡的主要外科手段之一。
转录组测序：此研究中涉及的miRNA-seq和mRNA-seq测序属于转录组测序。利用新一代高通量测序方法，对提取的生物样本总RNA进行深度测序，从而可以系统、全面地检测生物样本的基因表达谱信息。作为一种新兴、高效的研究手段，转录组测序技术为生物医学功能研究和机制探索提供了新的策略。

背景：胫骨横向骨搬移术已成为当前严重糖尿病足溃疡(WagnerIII级及以上)治疗的关键方法，然而确切的分子调控机制仍未阐明。
目的：构建胫骨横向骨搬移术治疗糖尿病足溃疡动物模型并进行转录组测序，识别差异表达显著的miRNA、关键靶基因并构建相应的miRNA-mRNA调控网络。
方法：建立兔糖尿病足溃疡创面并进行胫骨横向骨搬移术治疗，采集兔外周血进行miRNA-seq和mRNA-seq测序。对测序获得的表达谱数据进行差异表达分析以识别差异表达显著的miRNA和mRNA。使用TargetScan和miRNADA软件预测miRNA的靶基因并构建相应的miRNA-mRNA调控网络。对网络图中的靶基因进行京都基因与基因组百科全书富集分析、蛋白质相互作用分析，使用MCC和Degree算法筛选核心靶基因。
结果与结论：共识别9个显著差异表达的miRNA和2 667个显著差异表达的mRNA；依据差异分析结果和预测的miRNA靶基因数据，构建了包含7个miRNA和79个靶基因的miRNA-mRNA调控网络；京都基因与基因组百科全书富集分析发现这些靶基因主要参与代谢通路、内质网中的蛋白质加工、FoxO信号通路、丙酸代谢、N-聚糖生物合成等生物途径或信号通路；蛋白质相互作用分析揭示了这些靶基因表达蛋白之间的相互作用关系并将BAG3、AKT3、PPP4C、SEC61A1、DNAJC3、USP7、DAD1、SETD7鉴定为核心靶基因。结果表明，通过转录组测序鉴定出一系列与糖尿病足溃疡治疗相关的关键miRNA、靶基因和信号通路，不仅为糖尿病足溃疡治疗靶点选择提供了新候选，同时也为深入探索胫骨横向骨搬移术的治疗机制开辟了新方向。
https://orcid.org/0009-0006-4525-1956 (黄文良) 


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 胫骨横向骨搬移术, 糖尿病足溃疡, 转录组测序, miRNA, miRNA-mRNA调控网络

Abstract: BACKGROUND: Tibial transverse transport has emerged as a pivotal therapeutic approach for severe diabetic foot ulcers (Wagner grade III and above); however, its precise molecular regulatory mechanisms remain largely elusive.
OBJECTIVE: To establish an animal model of tibial transverse transport for diabetic foot ulcer treatment and perform transcriptome sequencing, aimed at identify significantly differentially expressed miRNAs and key target genes, as well as construct the corresponding miRNA-mRNA regulatory network.
METHODS: A diabetic foot ulcer wound model was established in rabbits and treated with tibial transverse transport. Peripheral blood samples were collected for miRNA-seq and mRNA-seq. Differentially expressed miRNAs and mRNAs were identified through bioinformatics analysis of sequencing data. Target genes of miRNAs were predicted using TargetScan and miRanda, and a miRNA-mRNA regulatory network was constructed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) analysis were performed on the target genes in the network. Core target genes were subsequently screened using the Maximal Clique Centrality and Degree algorithms.
RESULTS AND CONCLUSION: A total of 9 miRNAs and 2 667 mRNAs with significant differential expression were identified. Based on the differential analysis results and miRNA target gene predictions, a miRNA-mRNA regulatory network containing 7 miRNAs and 79 target genes was constructed. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these target genes were primarily involved in the metabolic pathway, protein processing in endoplasmic reticulum, FoxO signaling pathway, propanoate metabolism, N-glycan biosynthesis, and other signaling pathways. Protein-protein interaction analysis revealed the interaction between the expressed proteins of these target genes and identified BAG3, AKT3, PPP4C, SEC61A1, DNAJC3, USP7, DAD1, and SETD7 as the core target genes. This study identified a series of key miRNAs, target genes, and signaling pathways associated with the treatment of diabetic foot ulcers through transcriptome sequencing. These findings not only provide new candidate targets for treating diabetic foot ulcers but also open new avenues for further exploration of the therapeutic mechanisms of tibial transverse transport.


Key words: tibial transverse transport, diabetic foot ulcers, transcriptome sequencing, miRNA, miRNA-mRNA regulatory network

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