雷公藤红素抑制荷瘤裸鼠移植瘤血管生成作用地研究.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，周幽心谢学顺苏州大学附属第一医院神经外科雷公藤红素；碱性成纤维细胞生长因子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。每周两次免疫组化染色检测移植瘤组织中的MVD、bFGFVEGF、VEGFR1、VEGFR2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在移植瘤组织中均,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组雷公藤红素4mg/kg2mg/kg组均移植瘤组织中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。SHG44胶质瘤裸鼠的移植瘤生长，并存在剂量依赖性。bFGF、VEGFR1、VEGFR2有作用，对VEGF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：肿瘤组织中VEGFR阻止VEGF发挥效应抑制肿瘤血管生成bFGF的蛋白表达，对抑制肿瘤血管生成有作用。 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 expressions of microvessel density (MVD), basic fibroblast growth factor(bFGF) vascular endothelial growth factor(VEGF), vascular endothelial growth factor 1(VEGFR1), and vascular endothelial growth factor 2(VEGFR2) were detected in each paraffin imbedded xenograft of the mice by immunohistochemistry staining. Result: Compared with the control group, both two Celastrol-treated groups (4 mg/kg and 2 mg/kg