重组人骨形成蛋白复性探讨及重组人骨形成蛋白4二连体对辐射损伤小鼠造血系统的作用

发布时间：2018-06-29 15:14

本文选题：重组人骨形成蛋白2成熟肽 + 重组人骨形成蛋白4二连体　；参考：《第四军医大学》2006年硕士论文

【摘要】：骨形成蛋白(bone morphogenetic proteins，BMPs)属于TGF-β超家族成员，研究表明：BMPs不是一般的生长因子，而是一类多功能的细胞分化因子。BMP2和BMP4是骨形成蛋白家族中的两个重要成员，在结构和功能上很相似，在胚胎发育及各组织器官的形成过程中都起着非常重要的作用。BMP2和BMP4都能诱导骨骼发育和造血组织的分化。与BMP4相比，BMP2的诱骨活性更强，BMP2与成体骨骼系统的修复有重要关系，它可以诱导异位骨形成，对骨缺损和难治性骨不连具有很好的治疗前景，并且随着组织工程的发展，BMP2已经成为研究骨组织工程使用的重要诱导因子，使其在临床的应用前景更加广阔。与BMP2不同，BMP4的生物活性主要体现在对造血系统的作用上，在胚胎期它诱导中胚层的形成，对诱导造血系统的形成起关键作用，在成年个体中它可以诱导造血干细胞向三系造血细胞转化，是重要的诱血因子。以上均说明BMP2和BMP4这两种分化因子有所不同，都具有很好的临床应用前景。本文进行了三个部分的研究：进一步探讨了BMPs的复性方法；构建人骨形成蛋白4成熟肽二连体，并初步探讨辐射损伤造血后，它在造血系统修复中所起的作用。第一部分：重组人骨形成蛋白(rhBMP)复性与活性的探讨。目前基因工程制备BMPs的表达系统分为原核表达系统和真核表达系统。哺乳动物细胞表达的BMPs具有良好的生物活性，但表达量低，表达产物回收、纯化困难、生产成本很高，这就使得BMPs的价格非常昂贵，难以在临床广泛使用。原核表达系统，特别是大肠杆菌系统，是经典的表达系统，与真核表达系统相比，它具有表达效率高，容易操作，容易监控，产物稳定，生产成本低等优点。但原核表达系统所表达的蛋白质需要经过
[Abstract]:Bone morphogenetic protein (bone morphogenetic proteinsBMPs) is a member of TGF- 尾 superfamily. Studies show that BMP is not a normal growth factor, but a multifunctional cell differentiation factor. BMP2 and BMP4 are two important members of bone morphogenetic protein family. BMP2 and BMP4 can induce bone development and hematopoietic differentiation. Compared with BMP4, the osteoinductive activity of BMP2 is stronger. BMP2 has an important relationship with the repair of adult bone system. It can induce ectopic bone formation and has a good prospect for the treatment of bone defect and refractory nonunion. With the development of tissue engineering, BMP2 has become an important inducer in the study of bone tissue engineering. Different from BMP2, the biological activity of BMP4 is mainly reflected in its effect on hematopoietic system. It induces mesoderm formation in embryonic stage and plays a key role in the formation of hematopoietic system. It can induce the transformation of hematopoietic stem cells to three-line hematopoietic cells in adult individuals and is an important inducer. All of the above indicate that BMP2 and BMP4 are different differentiation factors and have a good clinical application prospect. In this paper, three parts were studied: the refolding method of BMPs, the construction of human bone morphogenetic protein 4 mature peptide disids, and the role of BMPs in hematopoietic repair after radiation injury. Part one: refolding and activity of recombinant human bone morphogenetic protein (rhBMP). The expression system of BMPs prepared by genetic engineering is divided into prokaryotic expression system and eukaryotic expression system. BMPs expressed in mammalian cells have good biological activity, but they are low in expression, difficult to recover, difficult to purify, and high in production cost, which makes BMPs very expensive and difficult to be widely used in clinical practice. Prokaryotic expression system, especially Escherichia coli system, is a classical expression system. Compared with eukaryotic expression system, it has the advantages of high expression efficiency, easy operation, easy monitoring, stable product and low production cost. But the protein expressed by the prokaryotic expression system needs to go through
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R341

【参考文献】