Zebularine和丁酸钠联合诱导兔骨髓间充质干细胞介入治疗兔急性肝功能衰竭实验研究

To improve the differentiation rate of hepatocytes from bone marrow mesenchymal stem cells and maintain their functions are the key factors for their transplantation in the treatment of liver failure. Research suggests that, epigenetic changes play an important role in the differentiation of stem cells. Based on the successful preparation of bone marrow mesenchymal stem cells, bone marrow mesenchymal stem cells transfected by VEGF gene, the liver cell differentiation successfully induced, transplantation in liver to improve liver function,the research group will use rabbit liver failure model,molecular biology, histocytology, pathology, immunology, interventional radiology, epigenetics and magnetic resonance techniques to dynamically observe the changes of location, migration,liver cell differentiation, immune function, liver function, hepatic morphology, tissue and cell structure,liver cell proliferation, apoptosis, necrosis, and functional status, hepatocyte growth factor, micro-angiogenesis and its regulation gene, DNA repair gene, DNA transcriptiongene and pluripotency transcription factor of bone marrow mesenchymal stem cells induced by combination of zebularine and sodium butyrate by percutaneous transhepatic injection and hepatic artery perfusion,respectively,on the molecular, cell, organ, and overall levels. The study has not been reported at home and abroad. If successful, it will open up a new way to treat liver failure in clinic and to improve the overall level of treatment of liver failure.

提高骨髓间充质干细胞肝细胞分化率并维持其功能是其移植治疗肝功能衰竭的关键因素。研究提示，表观遗传学改变在干细胞分化过程中扮演重要角色。本课题组在成功制备骨髓间充质干细胞、VEGF基因修辞骨髓间充质干细胞、诱导其肝细胞分化、肝内移植改善肝功能的基础上，拟通过兔肝功能衰竭模型，采用分子生物学、组织细胞学、病理学、免疫学、介入放射学、表观遗传学和磁共振学技术，在分子、细胞、器官和整体水平动态观察分别经皮肝穿刺注射和肝动脉灌注zebularine和丁酸钠联合诱导骨髓间充质干细胞的定位、迁移及肝细胞分化、肝功能、免疫功能、肝脏形态、组织及细胞结构、肝细胞增殖、凋亡、坏死及功能状态、促肝细胞生长因子、微血管生成及其调控基因、DNA修复基因、DNA 转录基因和多潜能性转录因子的变化。该研究在国内外未见报道，如获成功，将为肝功能衰竭临床治疗开辟一条新的途径，提高肝功能衰竭的整体治疗水平。