雷公藤红素抑制荷瘤裸鼠移植瘤血管生成作用的研究.docVIP

雷公藤红素抑制荷瘤裸鼠移植瘤血管生成作用的研究 姜华1，孙成法1，褚荣涛1，王君祥1，周幽心2，谢学顺2 （1 常熟市第二人民医院神经外科 215500；2苏州大学附属第一医院神经外科 215006） 关键词 雷公藤红素；胶质瘤；碱性成纤维细胞生长因子；血管内皮生长因子；血管内皮生长因子受体1；血管内皮生长因子受体2 摘要 目的：探讨雷公藤红素对荷SHG44胶质瘤裸鼠移植瘤生长及血管生成的作用机制。方法: 建立BALB/c裸小鼠SHG-44胶质瘤同种移植动物模型，将34只荷瘤裸鼠随机分为5组,采用腹腔内注射给药方法。雷公藤红素按三种浓度4mg/kg、2mg/kg、1mg/kg分组给药；阳性对照顺铂组按2mg/kg给药。每周两次，共给药四周。定期观察肿瘤生长情况测量肿瘤体积，计算抑瘤率。免疫组化染色检测移植瘤组织中的MVD、bFGF、VEGF、VEGFR1、VEGFR2的蛋白表达。结果: 与空白对照组相比，雷公藤红素4mg/kg组、雷公藤红素2mg/kg组均能抑制肿瘤生长(P ＜0.05)，其体积抑瘤率分别为35%、26.9%。VEGF蛋白表达在移植瘤组织中均可检测到,各组间无显著性差异。空白对照组中bFGF、VEGFR1、VEGFR2蛋白表达高且微血管计数(MVD)最多；雷公藤红素4mg/kg组下调荷瘤裸鼠移植瘤组织中bFGF的蛋白表达。雷公藤红素4mg/kg、2mg/kg组均能下调移植瘤组织中VEGFR1、VEGFR2的蛋白表达(Ｐ0.05)，微血管计数(MVD)也随之降低(Ｐ0.05)，呈剂量依赖关系。结论: 雷公藤红素能明显抑制荷SHG44胶质瘤裸鼠的移植瘤生长，并存在剂量依赖性。雷公藤红素对bFGF、VEGFR1、VEGFR2的蛋白表达有显著下调作用，对VEGF蛋白表达没有影响。雷公藤红素抑制荷SHG44胶质瘤裸鼠移植瘤生长的机制可能是：下调肿瘤组织中VEGFR蛋白表达，阻止VEGF发挥效应，抑制肿瘤血管生成；下调bFGF的蛋白表达，对抑制肿瘤血管生成有一定作用。 Antiangiogenic activity of Celastrol inhibits SHG44 glioma growth JIANG Hua1,SUN Cheng-Fa1,CHU Rong-Tao1,WANG Jun-Xiang1,ZHOU You-Xin2,XIE Xue-Shun2 1Department of Neurosurgery,The Second Hospital of Changshu,Changshu 215500; 2Department of Neurosurgery,Affiliated First Hospital,Soochow University,Suzhou 215006,China) Key word celastrol; glioma; basic fibroblast growth factor；vascular endothelial growth factor; vascular endothelial growth factor 1; vascular endothelial growth factor 2 ABSTRACT Aim: To investigate the effects and explore the mechanism of Celastrol on the angiogenesis and growth of SHG44 glioma cells in vivo.Methods: Animal models were established, in which 34 BALB/c nude mice were transplanted subcutaneously SHG44 glioma cells. The total mice were divided into five groups randomly, including the control group treated without drugs, a group with Cisplatin (2 mg/kg, ip five times weekly for four weeks), and three groups with different doses of Celastrol (4mg/kg, 2mg/kg and 1mg/kg, ip five times weekly for four weeks). The dimensions of xenografts were measured and the living states of the mice observed. The e