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慢性炎症对小鼠黑色素瘤血管生成的影响

房东亮1,马跃美1,赵秀兰2,孙涛2,3,刘艳荣4,王倩1,田原1   

  1. 1. 天津医科大学基础医学院外科手术学教研室
    2. 天津医科大学
    3.
    4. 天津医科大学病理教研室
  • 收稿日期:2012-08-17 修回日期:2012-10-26 出版日期:2013-03-15 发布日期:2013-03-15
  • 通讯作者: 马跃美

Influence of chronic inflammation on angiogenesis in mouse malignant melanoma

  • Received:2012-08-17 Revised:2012-10-26 Published:2013-03-15 Online:2013-03-15
  • Contact: MA Yue mei

摘要:

【摘要】目的 研究慢性炎症对小鼠恶性黑色素移植瘤的生长及其血管生成的影响。方法:60只C57BL小鼠随机分成3组,对照(C)组、炎症+肿瘤(I+T)组和单纯肿瘤(T)组。于小鼠背部皮下制作气囊并于鼠蹊部接种B16黑色素瘤细胞悬液,皮下气囊分别注入弗氏佐剂(CFA)或生理盐水;C组不做任何处理。肿瘤组织经CD31免疫组化染色后计数肿瘤组织中微血管数目(MVD)。留取小鼠血清,通过酶联免疫吸附试验(ELISA)检测血清中白细胞介素(IL)-6、 IL-17、IL-23及血管内皮细胞生长因子(VEGF)的含量。结果:建模后15~27 d时I+T组小鼠肿瘤体积和质量均大于T 组(P < 0.05或P < 0.01)。建模后9、15、21及27 d,I+T组小鼠肿瘤组织MVD大于T组,I+T组和T组小鼠血清4种因子含量均明显大于C组(P < 0.01),且除建模后第9 天I+T组血清IL-17、IL-23含量与T组差异无统计学意义外,其余各 I+T组血清IL-6、IL-17、IL-23及VEGF含量均大于T组(P < 0.05或P < 0.01)。结论:弗氏佐剂诱导的慢性炎症促进了小鼠黑色素瘤的生长,且炎症部位分泌的某些细胞因子会通过某种途径促进肿瘤血管的生成。

关键词: 黑色素瘤, 疾病模型, 动物, 炎症, 小鼠, 近交C57BL, 新生血管化, 病理性

Abstract: [Abstract] Objective  To investigate the influence of chronic inflammation on the growth and angiogenesis in mouse transplanted melanoma. Methods Sixty inbred C57BL mice were randomly divided into three groups,control group (C),inflammation + tumor group (I+T) and tumor group (T). The subcutaneous balloon was made on the mouse back, and the suspension of B16 melanoma cells was injected into the groin areas in both I+T group and T group. Either complete Freund adjuvant (CFA) or physiological saline was injected into the subcutaneous balloon of mice respectively. No intervention measures were taken in C group. Tumor tissues were stained with CD31 immunohistochemistry and the microvessel density (MVD) was counted. Enzyme-linked immunosorbent assays (ELISA) was used to detect the serum contents of interleukin (IL)-6, IL-17, IL-23 and vascular endothelial growth factor (VEGF) in three groups. Results  The tumor volumes and weights were significantly larger in I+T group than those in T group from 15 days to 27 days after model establishment (P < 0.05 orP < 0.01). The values of MVD in tumor tissues were significantly higher in I+T group than those in T group 9, 15, 21 and 27 days after model estab lishment (P < 0.01). The serum levels of IL-6, IL-17, IL-23 and VEGF were significantly higher in I+T group and T group than those of C group (P < 0.01). The serum levels of IL-6, IL-17, IL-23 and VEGF were significantly higher in I+T group than those of T group except for the 9-day after model establishment (P < 0.05 orP < 0.01). Conclusion The chronic inflammation induced by CFA can promote the development of mouse melanoma. And tumor angiogenesis could be promoted by some cytokines secreted by inflammatory cells. 

Key words: melanoma disease models, animal inflammation mice, inbred C57BL neovascularization, pathologic Vascular Endothelial Growth Factors interleukins, 病理性