中国组织工程研究

中国组织工程研究

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

人脐带间充质干细胞移植肝硬化大鼠肝脏miRNA的差异表达

刘祥忠1，邹志强1，王贵强2，李  栋3，邵志英1   

  1. 1烟台市传染病医院，山东省烟台市  264001； 
    2北京大学第一医院，北京市  100034； 
    3山东大学齐鲁医院，山东省济南市  250012
  • 出版日期:2015-06-04 发布日期:2015-06-04
  • 通讯作者: 李栋，博士，副主任技师，山东大学齐鲁医院，山东省济南市 250012
  • 作者简介:刘祥忠，男，1971年生，山东省蓬莱市人，汉族，2003年佳木斯大学毕业，硕士，副主任医师，主要从事各种肝炎的基础与临床研究。
  • 基金资助:

    济南市2014科学技术发展计划(201403010)

MicroRNA differential expression in liver cirrhosis rats undergoing human umbilical cord mesenchymal stem cell transplantation 

Liu Xiang-zhong1, Zou Zhi-qiang1, Wang Gui-qiang2, Li Dong3, Shao Zhi-ying1   

  1. 1Hospital of Infectious Diseases of Yantai, Yantai 264001, Shandong Province, China; 
    2Peking University First Hospital, Beijing 100034, China; 
    3Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
  • Online:2015-06-04 Published:2015-06-04
  • Contact: Li Dong, M.D., Associate chief technician, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
  • About author:Liu Xiang-zhong, Master, Associate chief physician, Hospital of Infectious Diseases of Yantai, Yantai 264001, Shandong Province, China
  • Supported by:

    the Scientific Research Development Plan of Jinan City in 2014, No. 201403010

PDF

394

被引次数

2

摘要：

背景：研究表明脐带间充质干细胞可以显著改善肝硬化的程度，进而修复肝损伤，但其治疗肝硬化的分子调控机制，尤其是非编码RNA调控的肝内基因变化，目前并没有得到详细的阐释。
目的：分析人脐带间充质干细胞移植肝硬化大鼠肝细胞中微小RNA基因表达的变化。
方法：采用四氯化碳皮下注射联合乙醇喂服方法建立肝硬化大鼠模型，造模8周后经尾静脉输注人脐带间充质干细胞，每周1次，连续注射4周。最后一次注射治疗1周后收集大鼠肝脏组织进行石蜡切片和提取肝脏RNA进行表达谱基因芯片分析，同时收集血清利用自动生化分析仪测定肝功能指标变化。
结果与结论：人脐带间充质干细胞治疗可以显著降低谷丙转氨酶、谷草转氨酶和转肽酶水平，脂肪病变和肝细胞坏死显著减少。微小RNA表达谱芯片杂交分析和PCR验证结果显示rno-miR-369-5p、rno-miR-3584-5p和rno-miR-153*这3种微小RNA基因在造模过程中先下调表达，并在人脐带间充质干细胞治疗后显著上调；而rno-miR-93、rno-miR-199a-3p、rno-miR-195、rno-let-7a和rno-miR-19a这5种微小RNA基因在造模过程中先上调表达，并在人脐带间充质干细胞治疗后显著下调。以上结果表明人脐带间充质干细胞逆转肝硬化和肝细胞损伤过程中，可能通过上调rno-miR-369-5p、rno-miR-3584-5p和rno-miR-153*等miRNA基因表达，下调rno-miR-93、rno-miR-199a-3p、rno-miR-195、rno-let-7a和rno-miR-19a等相关miRNA基因表达发挥治疗作用。

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: 干细胞, 移植, 肝硬化, 脐带间充质干细胞, 细胞治疗, 微小RNA

Abstract:

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) can obviously relieve liver cirrhosis, and thereby repair liver injury. However, the molecular mechanism of hUC-MSCs therapy for liver cirrhosis is limited at present, and especially the non-coding RNA regulation of hepatic gene changes has not been detailed.
OBJECTIVE: To investigate the changes of microRNA after hUC-MSCs therapy in rats with liver cirrhosis.
METHODS: Liver cirrhosis models were established in rats using carbon tetrachloride subcutaneous injection 
plus oral administration of alcohol. At 8 weeks after modeling, hUC-MSCs were injected via the tail vein once a week for 4 consecutive weeks. At 1 week after the last injection, rat liver tissues were collected for paraffin embedding. Liver RNA was extracted for gene chip analysis. Blood samples were collected and analyzed using an automatic biochemical analyzer to detect the changes of liver function.
RESULTS AND CONCLUSION: Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transpeptidase were improved significantly after hUC-MSCs therapy. Fat lesions and necrosis of hepatocytes were significantly reduced. MicroRNA expression microarray hybridization analysis and PCR results showed that rno-miR-369-5p, rno-miR-3584-5p and rno-miR-153* were down-regulated during modeling and increased after hUC-MSCs therapy. And rno-miR-93, rno-miR-199a-3p, rno-miR-195, rno-let-7a and rno-miR-19a were firstly up-regulated in the process of modeling and then down-regulated obviously after hUC-MSCs therapy. These results suggest that hUC-MSCs may reverse liver cirrhosis and liver cell damage through up-regulation of rno-miR-369-5p, rno-miR-3584-5p and rno-miR-153*, and down-regulation of rno-miR-93, rno-miR-199a-3p, rno-miR-195, rno-let-7a and rno-miR-19a.  

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

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