Biomechanical study on the process of neovascularization in tumor tissues

肿瘤组织的生长以肿瘤组织内和周围明显的血管生成为特征，因为肿瘤细胞基本上需要营养物质和氧气的供应，以及肿瘤产生的废物代谢物的清除。因此，需要对肿瘤微循环中的血管生成过程和血流动力学有详细的了解，以获得合理的恶性肿瘤诊断和治疗指南。为了能够在生理条件下观察肿瘤的微血管，我们建立了扩散到大鼠腹膜腔的实体瘤模型。为了分析肿瘤微血管构筑和血流动力学的定量特征，我们进行了一系列实验。为了制备腹膜播散性肿瘤模型，将结肠癌细胞系(RCN-9)的1x107细胞接种到雄性Fischer 344大鼠的腹膜腔内。接种肿瘤细胞4~11d后，活体显微镜观察大鼠肠系膜微循环，根据Horton分叉定律分析血管网络的分支模式。伴随着肿瘤的生长，肠系膜窗可见明显的新生血管。新生血管主要发生在静脉系统，静脉系统的分支模式更加复杂。在肠系膜微血管系统测量了血流动力学参数，即血管直径和血流速度。在荷瘤大鼠的微血管中，与与肿瘤无解剖关系的微血管相比，供瘤小动脉和引瘤小静脉明显扩张，血流速度减慢。

Growth of the tumor tissue is characterized by a marked asgiogenesis in and around the tumor tissues, since tumor cells essentially require supply of nutrients and oxygen and removal of waste metabolites produced by the tumor. Thus, detailed knowledge of the angiogenic process and hemodynamics in the tumor microcirculation is needed to obtain sound guidelines for diagnosis and treatment of malignant tumors. To enable observation of the tumor microvasculature under physiological conditions, we have established a solid-tumor model disseminated into the peritoneal cavity of the rat. We have performed a series of experiments to analyze quantitative features of the vascular architecture of the tumor microvasculature and hemodynamics of the blood flow.To prepare peritoneal disseminated tumor model, 1x107 cells of a colon cancer cell line (RCN-9) were inoculated into peritoneal cavity of male Fischer 344 rats. Four to eleven days after the tumor cell inoculation, the rat was subjected to intravital microscopic observation of the mesenteric microcirculation.The branching pattern of the vascular network was analyzed based on the Horton's law of bifurcation. Accompanied with tumor growth, mesenteric windows showed a marked neovascularization. The neovascularization occurred predominantly in the venular system and the branching pattern of the venular system bacame more complicated.Hemodynamic parameters, i. e.vassel diameter and blood flow velocity, were measured in the mesenteric microvasculature. In microvasculatures of the tumor-bearing rats, the tumor-feeding arterioles and tumor-draining venules were significantly dilated and showed decreased blood flow velocity compared with the microvessels that have no anatomical connection with the tumor.