携绿色荧光蛋白的人低氧诱导因子1α及其突变型重组腺病毒载体的构建及鉴定

发布时间：2018-01-03 06:27

本文关键词：携绿色荧光蛋白的人低氧诱导因子1α及其突变型重组腺病毒载体的构建及鉴定　出处：《第一军医大学》2006年硕士论文　论文类型：学位论文

【摘要】：背景缺血性心脏病目前常规治疗包括药物治疗、冠脉介入(PCI)及冠脉旁路移植术(CABG)，然而相当一部分患者药物治疗难以见效，也不适于常规血管再通术处理，另外还有些患者经过上述处理后仍然存在冠脉再狭窄、心肌微、小血管功能障碍、心功能低下，因此必须寻求其它方法。近年来，随着分子生物学的巨大进步，基因治疗促缺血心肌血管新生已成为冠脉血运重建术中具有发展前景的新方向，目前血管新生是生物学界基因治疗发展最快的领域。促血管生长因子研究较多的有VEGF、FGF等，虽然Ⅰ期临床试验结果证明安全有效，但Ⅱ期临床试验结果并不理想，资料显示VEGF可导致新生血管组织水肿、血管通透性增高、易发生炎症反应等，甚至可能促进动脉硬化进展，毛细血管过度增殖及血管瘤形成等，FGF治疗则与蛋白尿有关。血管生长过程本身受一系列生长因子的调节，是个复杂的过程，单个生长因子治疗并不足以诱导成熟的血管新生。低氧诱导因子-1(hypoxia inducible factor 1，，HIF-1)是细胞对缺氧作出适应性反应的上游关键性转录因子，通过对VEGF、Ang、EPO、PDGF、HO-1等60多种靶基因的转录调控参与了血管新生、红细胞生成等病理生理过程。临床前期研究表明，应用具有组成型表达活性的HIF-1α基因治疗可诱导生理功能完整的血管新生。HIF-1α诱导的新生血管具有无明显炎症反应、不渗漏、不引起组织水肿的特点，此外，HIF-1α还可以促进EPO、HO-1、INOS等基因的转录，具有抗细胞凋亡、改善心肌细胞代谢等血管新生以外的作用。因此，人们对HIF-1
[Abstract]:Background At present, the routine treatment of ischemic heart disease includes drug therapy, coronary intervention (PCI) and coronary artery bypass grafting (CABGG). In addition, some patients still have coronary restenosis, myocardial micromyocardium, small vascular dysfunction and low cardiac function after the above treatment. In recent years, with the great progress of molecular biology, gene therapy to promote ischemic myocardial angiogenesis has become a new direction in coronary artery revascularization. At present, angiogenesis is the fastest growing field of gene therapy in biological field. VEGFFFFGF is the most important factor in the study of vascular growth factors, although the results of phase I clinical trials prove that it is safe and effective. However, the results of stage II clinical trials were not satisfactory. The data showed that VEGF could lead to edema of neovascularization tissue, increase of vascular permeability and inflammation, and might even promote the progression of arteriosclerosis. The treatment of capillary hyperproliferation and angioma formation is related to proteinuria. Vascular growth itself is regulated by a series of growth factors and is a complex process. The treatment of single growth factor was not enough to induce mature angiogenesis. Hypoxia inducible factor-1 hypoxia inducible factor 1. HIF-1) is the upstream key transcription factor of cell adaptive response to hypoxia. Transcriptional regulation of more than 60 target genes such as HO-1 is involved in angiogenesis, erythropoiesis and other pathophysiological processes. HIF-1 伪 gene therapy with constitutive expression activity can induce angiogenesis with intact physiological function. HIF-1 伪 induced neovascularization has no inflammatory reaction and no leakage. In addition, HIF-1 伪 can promote the transcription of EPO-HO-1 and INOS, and has anti-apoptosis. Improve cardiomyocyte metabolism and other angiogenic effects other than. Therefore, people on the HIF-1
【学位授予单位】：第一军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R341

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