局部热化疗对大鼠胶质细胞移植瘤血管再生及VEGF表达的影响

The effects of localized thermochemotherapy on angiogenesis and the expression of VEGF protein of C6 gliomas in rat

目的 研究局部热化疗对鼠胶质细胞移植瘤血管再生及血管内皮生长因子 (VEGF)表达的影响 ,探讨其治疗胶质瘤的机制。方法 在鼠胶质细胞移植瘤动物模型上 ,分组进行局部热疗、化疗和热化疗。用FⅧ RA染色标记血管内皮细胞 ,以微血管密度作为定量检测指标。用免疫组化S P法检测VEGF蛋白表达 ;电镜观察肿瘤微血管结构的变化。结果 热疗、化疗、热化疗组与对照组比较 ,VEGF蛋白表达减低(P <0 .0 1) ,且热化疗有协同作用 (P <0 .0 1)。VEGF表达与MVD间呈正相关 (r=0 .9798,P <0 .0 0 1)。热化疗后肿瘤微血管外径变小 ,血管壁变厚 ,血管减少 ,血管内皮细胞紧密连接增多 ,细胞连接间隙减小 ,有的血管甚至只能发现完整的基膜而缺乏内皮细胞。结论 ①热疗、化疗和热化疗能抑制肿瘤血管再生 ,且阿霉素与热疗有协同作用 ;②热化疗能降低肿瘤VEGF合成与分泌 ,破坏与减少肿瘤血管再生 。

Objective To study the effects of localized thermochemotherapy on angiogenesis and the expression of VEGF protein of C6 gliomas in rats,and explore the mechanisms of angiogenesis inhibition by localized thermochemotherapy. Methods Following the establishment of animal models, 40 rats harboring the C6 gliomas were randomly allocated to 4 groups,the rats in the fore 3 groups were treated by localized thermochemotherapy, hyperthermia and chemotherapy, respectively, the remaining group served as control. The expression of VEGF and FⅧ RA protein were detected by S P immunohistochemistry. The vascular structure in rat's glioma was observed by immunohistochemistry and electron microscopy technique. Results As compared with the control group, the expression of VEGF protein was decreased in the hyperthermia and chemotherapy groups,as well as in the thermochemotherapy group.The expression of VEGF was positively correlated with the microvessel density in the tumor ( r =0.9798, P <0.001). Electron microscopic observation also showed that angiogenesis was inhibited by interstitial localized thermochemotherapy in rat's gliomas. Conclusion Hyperthermia, chemotherapy and thermochemotherapy could inhibit angiogenesis in tumor.The chemotherapy agent adriamycin (ADM) showed remarkable synergic effects with hyperthermia in C6 glioma of rat. Both the synthesis and secretion of VEGF could be inhibited by thermochemotherapy.