内皮抑素对卵黄囊瘤裸鼠模型血管生长的影响

Effects of Endostatin Treatment on Yolk Sac Tumor Xenografts of Children in Nude Mice

目的通过动物实验验证血管生长在卵黄囊瘤裸鼠模型中的作用,以及内皮抑素对模型血管生长的影响。方法建立卵黄囊瘤裸鼠模型,分别采用1.5mg/(kg.d)及0.75mg/(kg.d)两个浓度重组人血管内皮抑制素局部注射干预,并皮下及瘤内注射生理盐水25ml/(kg.d)注射对照,共14天,每组10只。药物干预结束后,明胶-氧化铅悬浊液灌注法行肿瘤血管造影,观察肿瘤血管差异。免疫组化方法检测移植瘤AFP、VEGF、CD34。结果 (1)小儿恶性畸胎瘤裸鼠模型复制成功,AFP在移植瘤细胞胞质中有表达,肿瘤性质稳定。(2)肿瘤体积自第6天测量治疗组肿瘤生长速度明显低于对照组(P<0.05);第12天测量结果提示高剂量组与低剂量组肿瘤体积出现显著差异(P<0.01)。(3)免疫组化:VEGF表达范围及强度,治疗组均小于对照组(P<0.05),高剂量组小于低剂量组(P<0.05),两对照组之间无明显差异(P>0.05);MVD:治疗组均小于对照组(P<0.01),高剂量组小于低剂量组(P<0.01),两对照组之间无明显差异(P>0.05)。(4)肿瘤血管造影:血管分布密度内皮抑素高剂量治疗组<低剂量组<实验对照组。结论内皮抑制素通过抑制VEGF的作用,减少血管发生,从而对卵黄囊瘤裸鼠模型移植瘤的生长有抑制作用。

Objective Based on the establishment of Yolk Sac tumor xenografts of children in nude mice, we study the effects and mechanism of endostatin （ES） on YST＇S tumor xenografts of children. Methods Fourty nude mice were inoculated with tissue of YST＇S xenograft and five males and five feamales for each group. In high - dose （HD） group,nude mice bearing cancer would be subcutaneouly and intratumorally injected ES by 1.5rag/（ kg - d） for 14 days. In low -dose （LD） group,mice would be injected ES by O. 75rag/（ kg·d） for 14 days. In experimental control group,mice be injected isotonic Nachloride by 25ml/（ kg·d） for 14 days. And in blank control group, mice would not be injected. The volume of transplantation tumors was measured everyday. Tumor control rate and draw growth curve were detected. The differences of the tumor vessel between each group were obsorved. The expression of AFP and level of VEGF and MVD also be measured by immunohistochemistry. Results The duplication of malignant teratoma xenografts of children in nude mice was successful, and the quale of the transplantation tumors is steady. The speed of tumor growth of treatment groups was slower than control groups since the sixth day（ P 〈 0.05 or P 〈 0.01 ）. Measurements on the 12th day shown that the contrast of gross tumor volume between HD group and LD group was significant（P 〈 0.01 ）. There were no significant deviation between experimental control group and blank control group on any time point （P 〉 0.05）. Treatment groups were lower than control groups in extent and magnitude of expression of VEGF（P 〈0.05 ）. And there was no significant deviation between experimental control group and blank control group（ P 〉 0.05 ）. For M VD, treatment groups were fewer than control groups （P 〈 0.01 ）. H D group was fewer than LD group（ P 〈 0.01 ） , and there was no sig- nificant deviation between experimental control group and blank control group（ P 〉 0.05）. Angiography of tumor showed that vascular dis- tribution density was HD group 〈 LD group 〈 experimental control. Conclusion Endostatin could hindrance the effect of VEGF,thus to control angiogenesis,which thereby effectively iahibit YST＇S xenografts of children in nude mice.