肿瘤相关性恶液质：VEGF作用机制的实验研究  

Cancer-Associated Systemic Syndrome(CASS):The Mechanism of VEGF in Tumor-Bearing Mice

作　　者：陈芳[1] 薛远 曹义海 韩宝惠[1] 

机构地区：[1]上海交通大学附属胸科医院肺内科,上海200030 [2]瑞典卡洛林斯卡医学院

出　　处：《中国肺癌杂志》2009年第4期283-288,共6页Chinese Journal of Lung Cancer

基　　金：国家留学基金委全额资助项目(No.【2007】3021) 资助~~

摘　　要：背景与目的VEGF在肿瘤发展中起着重要的作用,是肿瘤治疗的靶点之一。本研究目的是观察VEGF高表达的荷瘤小鼠各脏器的病理改变,并探讨VEGF在肿瘤相关性恶液质发展过程中的作用。方法将鼠源性纤维肉瘤细胞T241-VEGF和T241-Vector注射至小鼠背侧皮下,制备移植瘤模型,观察荷瘤小鼠一般情况,记录生存时间,检测血红蛋白和红细胞,测定血清hVEGF含量,病理学检查肝脏、脾脏、肾上腺、骨髓情况,共聚焦显微镜观察皮下肿瘤血管形态学变化。结果VEGF组荷瘤小鼠出现严重的贫血、体重减轻和肝脾肿大等恶液质表现,生存率明显下降。外周血红细胞和血红蛋白明显下降,血清VEGF却明显升高。肝脏、脾脏、肾上腺和骨髓的组织病理学检测异常,移植瘤血管形态迥异。结论肿瘤分泌的VEGF作用于荷瘤小鼠的多种组织和器官,表现为典型恶液质症状。提示VEGF参与荷瘤小鼠肿瘤相关性恶液质的发生和进展,为临床应用抗VEGF治疗肿瘤相关性恶液质提供了新的理论依据,更为晚期肿瘤患者联合抗VEGF治疗奠定了实验基础。Background and objective VEGF plays an important role in the development of cancer. The aim of this study is to observe the structural alterations in multiple organs of high VEGF expression mice, and insight into the role of tumor-derived VEGF in the development of CASS. Methods Murine fibrosarcoma of T241-VEGF and T241- Vector tumor cells were transplanted subcutaneously in mice to construct the xenografl tumor model. The mice gross examinations were observed and the percentage of survival animals in each group is presented. The level of hemoglobin, the numbers of erythrocytes and serum concentration of VEGF in peripheral blood were analyzed. Histological analysis of liver, spleen, adrenal gland and bone-marrow were applied. Vascular networks in tumors were analyzed under a confocal microscope. Results The VEGF-expressing tumor bearing mice manifested CASS by severe anemia, hepatosplenomegaly and loss of body weight. The survival rate of mice was decreased. The level of hemoglobin and erythrocytes in circulating blood were significantly reduced （P〈0.01）, with the increased serum concentration of VEGF. The blood vessels of tumor appeared as primitive and dilated sinusoidal vascular structures. Conclusion The tumor-produced VEGF affect multiple tissues, organs and resulted in CASS in mice model. It suggest that VEGF might be involved in the occurrence and development of CASS. It might be helpful for anti-VEGF therapy in clinical CASS and combing anti-VEGF therapy in advanced cancer patients.

关 键 词：血管内皮生长因子 肿瘤 恶液质 

分 类 号：R730.5[医药卫生—肿瘤]