【作者】 吴景文；

【导师】 章翔； 费舟；

【作者基本信息】 第四军医大学 ， 外科学， 2000， 博士

【摘要】 血管生成（angiogenesis）是指从已存在的血管床中产生出新生血管系统的复杂过程。这一过程受控于多种血管生成因子和抑制因子。正常血管形成被严格限定于某些特定短暂的生理过程，如胚胎发生和伤口愈合等；而持续的血管生成则是某些病理改变的特征，如肿瘤血管生成。肿瘤细胞是肿瘤血管生成的组织者，它能过量表达几种促血管生长因子，如血管内皮细胞生长因子（vascular endothelial growth factor, VEGF）、成纤维细胞生长因子（fibroblast growth factor, FGF）和血管产生素（angiopoietin）等；分泌多种酶，如尿激酶（urokinase-type plasminogen activator, u-PA）和基质金属蛋白酶（matrix metalloproteinase, MMP）；从细胞外基质中调动所需要的蛋白和酶，如整合素α_vβ₃（integrin α_vβ₃）和整合素α_vβ₅（integrin α_vβ₅）；征募宿主细胞，如巨噬细胞、淋巴细胞、纤维细胞，使它们分泌促血管生长因子。各类促血管生长因子过量表达和血管生成抑制因子下调是导致肿瘤血管增生，引起肿瘤生长和转移的基础。 研究表明，实体瘤生长和转移依赖于血管生成。肿瘤形成早期（血管前期），没有血管生长，此期肿瘤不超过0.4mm³，呈缓慢的线性生长。当肿瘤大小超过0.4mm³时（血管期），肿瘤开始形成自身的血管系统，并呈快速的近指数生长，其特征是肿瘤生长加速，并依赖于肿瘤血管床延伸出现远处转移。因此，在“血更多还原

【Abstract】 Angiogenesis, the formation of new capillary blood vessels from pre-existing ones, is a complicated process, which is controlled by many angiogenesis stimulating factors and inhibitory factors. Normal angiogenesis is strictly limited to some special transient physiological processes, such as embryogenesis, wound repair, and etc. But continuous angiogenesis is the characteristic of some pathlogical changes, such as tumor angiogenesis.The tumor cell is the organizer for its angiogenesis.It can overexpress several angiogenesis stimulating factors（such as VEGF , FGF , angiopoietin and etc）, secrete many enzymes（such as uPA and MMP）, mobilize the needed proteins and enzymes from the cell matrix（such as integrin α_v β₃ and α_v β₅）, recruit the host cells to secrete promoting angiogenesis factors（macrophage, lymphocyte and fibroblast）. Both upregulation of angiogenic stimulators and downregulation of angiogenesis inhibitors result in tumor blood vessel proliferation, which is the bases of the tumor growth and metastasis.Direct experimental evidences show that solid tumor growth and metastasis require new blood vessels. An avascular tumor （vascular prophase） rarely grows to a size larger than 0.4 mm³ and grows at a slow linear growth speed. Once a tumor更多还原