hif1α促成骨细胞il6 il8表达分子机制的研究 国家自然科学基金资助项目81273520-research on molecular mechanism of hi f1 α promoting il 6 il 8 expression in bone cells funded by national natural science foundation 8127520.docxVIP

目录中文摘要········································································································1英文摘要········································································································3英文缩写········································································································6研究论文HIF-1α促成骨细胞IL-6、IL-8表达分子机制的研究前言··········································································································8材料与方法·····························································································11结果·········································································································35附图·········································································································38讨论·········································································································48结论·········································································································52参考文献·································································································53综述低氧诱导因子调控机制的相关研究进展·······································57致谢···············································································································66个人简历·······································································································67HIF-1α促成骨细胞IL-6、IL-8表达分子机制的研究摘要目的：在骨组织生长发育及修复的过程中，机体血液供应起着至关重要的作用。低氧是促进血管生成的主要驱动力，它通过抑制低氧诱导因子（hypoxia-induciblefactor）-1α的降解，使其聚积并转运至细胞核内与HIF-1β结合形成HIF-1复合物，作为转录因子与低氧反应元件（hypoxiareactionelement,HRE）结合，进而激活下游靶基因血管内皮生长因子（vascularendothelialgrowthfactor,VEGF）的转录，从而促进血管的生成。在生理和病理条件下，由于骨组织血供的减少会使骨系细胞处于低氧状态，成骨细胞位于骨小梁的表面，其首先感受骨组织内血流的变化和氧压力的降低。本实验室前期研究发现，低氧及模拟低氧条件下，人成骨样MG-63细胞HIF-1α及下游靶基因VEGF的表达水平显著增加。白细胞介素（Interleukin-6，IL）-6和IL-8作为前血管生成因子，在血管发生发展中也起重要调节作用，而成骨细胞均可分泌这两种细胞因子。由此，我们推测HIF-1α也可能调节IL-6和IL-8的表达而在骨形成耦联血管生成过程中发挥重要作用。本文在前期工作的基础上，继续利用人成骨样MG-63细胞作为研究模型，探讨HIF-1α对成骨细胞IL-6、IL-8表达的作用及作用机制。方法：通过逆转录聚合酶链式反应（r