人脐带间充质干细胞移植肝硬化大鼠肝脏miRNA的差异表达
发布时间：2018-11-02 07:27
【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-mi R-369-5p、rno-mi R-3584-5p和rno-mi R-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-mi R-93、rno-mi R-199a-3p、rno-mi R-195、rno-let-7a和rno-mi R-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-mi R-3584-5p和rno-mi R-153*等miR NA基因表达,下调rno-miR-93、rno-mi R-199a-3p、rno-mi R-195、rno-let-7a和rno-mi R-19a等相关miR NA基因表达发挥治疗作用。
[Abstract]:Background: studies have shown that umbilical cord mesenchymal stem cells can significantly improve the degree of liver cirrhosis and repair liver injury, but its treatment of liver cirrhosis molecular regulatory mechanism, especially the non-coding RNA regulation of intrahepatic gene changes. At present, there is no detailed explanation. Aim: to investigate the changes of RNA gene expression in hepatocytes of cirrhotic rats transplanted with human umbilical cord mesenchymal stem cells. Methods: the rat model of liver cirrhosis was established by subcutaneous injection of carbon tetrachloride (CCL 4) combined with ethanol administration. After 8 weeks, human umbilical cord mesenchymal stem cells were infused via tail vein once a week for 4 weeks. One week after the last injection, the rat liver tissue was collected for paraffin section, RNA was extracted for gene chip analysis, and the serum was collected to determine the changes of liver function by automatic biochemistry analyzer. Results and conclusion: human umbilical cord mesenchymal stem cell therapy can significantly reduce the levels of alanine aminotransferase, alanine aminotransferase and transpeptidase, fatty lesions and hepatocyte necrosis. The results of microarray hybridization and PCR verification showed that rno-mi R-369-5pno-mi R-3584-5p and rno-mi R-153* were down-regulated in the process of modeling, and the results of microarray hybridization and PCR verification showed that the expression of rno-mi R-369-5pno-mi R-3584-5p and rno-mi R-153* were down-regulated. It was significantly up-regulated after treatment with human umbilical cord mesenchymal stem cells. However, rno-mi R-93rno-mi R-199a-3pnrno-mi R-195 rno-let-7a and rno-mi R-19a up-regulated the expression of RNA genes during the modeling process, and down-regulated significantly after treatment with human umbilical cord mesenchymal stem cells. These results suggest that human umbilical cord mesenchymal stem cells may down-regulate rno-miR-93, by up-regulating the expression of miR NA genes such as rno-miR-369-5p,rno-mi R-3584-5p and rno-mi R-153* in the process of reversing liver cirrhosis and hepatocyte damage. The expression of miR NA genes such as rno-mi R-199a-3pno-mi R-195rno-let-7a and rno-mi R-19a plays a therapeutic role.
【作者单位】： 烟台市传染病医院;北京大学第一医院;山东大学齐鲁医院;
【基金】：济南市2014科学技术发展计划(201403010)~~
【分类号】：R575.2
[Abstract]:Background: studies have shown that umbilical cord mesenchymal stem cells can significantly improve the degree of liver cirrhosis and repair liver injury, but its treatment of liver cirrhosis molecular regulatory mechanism, especially the non-coding RNA regulation of intrahepatic gene changes. At present, there is no detailed explanation. Aim: to investigate the changes of RNA gene expression in hepatocytes of cirrhotic rats transplanted with human umbilical cord mesenchymal stem cells. Methods: the rat model of liver cirrhosis was established by subcutaneous injection of carbon tetrachloride (CCL 4) combined with ethanol administration. After 8 weeks, human umbilical cord mesenchymal stem cells were infused via tail vein once a week for 4 weeks. One week after the last injection, the rat liver tissue was collected for paraffin section, RNA was extracted for gene chip analysis, and the serum was collected to determine the changes of liver function by automatic biochemistry analyzer. Results and conclusion: human umbilical cord mesenchymal stem cell therapy can significantly reduce the levels of alanine aminotransferase, alanine aminotransferase and transpeptidase, fatty lesions and hepatocyte necrosis. The results of microarray hybridization and PCR verification showed that rno-mi R-369-5pno-mi R-3584-5p and rno-mi R-153* were down-regulated in the process of modeling, and the results of microarray hybridization and PCR verification showed that the expression of rno-mi R-369-5pno-mi R-3584-5p and rno-mi R-153* were down-regulated. It was significantly up-regulated after treatment with human umbilical cord mesenchymal stem cells. However, rno-mi R-93rno-mi R-199a-3pnrno-mi R-195 rno-let-7a and rno-mi R-19a up-regulated the expression of RNA genes during the modeling process, and down-regulated significantly after treatment with human umbilical cord mesenchymal stem cells. These results suggest that human umbilical cord mesenchymal stem cells may down-regulate rno-miR-93, by up-regulating the expression of miR NA genes such as rno-miR-369-5p,rno-mi R-3584-5p and rno-mi R-153* in the process of reversing liver cirrhosis and hepatocyte damage. The expression of miR NA genes such as rno-mi R-199a-3pno-mi R-195rno-let-7a and rno-mi R-19a plays a therapeutic role.
【作者单位】： 烟台市传染病医院;北京大学第一医院;山东大学齐鲁医院;
【基金】：济南市2014科学技术发展计划(201403010)~~
【分类号】：R575.2
【参考文献】
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1 赵振强;陈志斌;蔡美华;王淑荣;陈蓉;王W，
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