蜂毒素对裸鼠骨肉瘤治疗作用及安全性的实验研究

Experimental Study of Treatment and Safety of Melittin on Xenotransplanted Models of Nude Mice

目的:观察蜂毒素对骨肉瘤裸鼠移植瘤生长抑制作用及毒副反应。方法:建立裸鼠骨肉瘤原位移植瘤模型,随机分4组:生理盐水组,蜂毒素低、高剂量组,顺铂组。观察各组裸鼠骨肉瘤的体积和体质量抑制率;放射免疫法测定血清碱性磷酸酶活性;测定外周血常规、骨髓有核细胞数目;光镜观察心肝脾肺肾及肿瘤的病理组织学情况;电镜观察肿瘤细胞的微细结构。结果:蜂毒素低剂量组肿瘤体积和体质量抑制率分别为42.98%、39.03%,高剂量组分别为67.54%、48.66%,蜂毒素能明显降低血清AKP水平;光镜与电镜下蜂毒素能诱导骨肉瘤细胞凋亡或坏死;高剂量蜂毒素给药后可见扭体动作、精神不振、萎靡少动等毒性反应,肾脏病理切片可见肾小管间质扩张充血,肾细胞间隙炎性细胞集聚。蜂毒素各组骨髓及心肺肝脾等脏器未造成明显毒副反应。结论:蜂毒素具有抑制骨肉瘤裸鼠移植瘤生长的作用,并能促使肿瘤细胞凋亡或坏死,无明显的毒副作用。

Objective：To study the antitumor effects and toxic and side effects of Melittin on xenotransplanted models of nude mice.Methods：Xenotransplanted models of SD rat osteosarcoma cell UMR-106 in the laevo-hind tibia of nude mice were established.Inoculated mice were randomly divided into normal saline group,positive controlgroup,low and high dose Melittin group.All the nude mice were sacrificed after treatment,the size and weight of tumor were measured and the tumor volumes and the inhibition rates of tumor were calculated,and peripheral blood cells,alkaline phosphatase and medullary karyote in one femur of nude mice were counted by hematology analyzer.Tumor tissues,myocardium,lung,liver,spleen,kidney and brain were sectioned,stained with hematoxylin and eosin,and then observed by light and electron microscope.Results：The mice treated with high dose Melittin groups showed significantly smaller volume and weight of tumor than those of NS group after treatment.AKP of Melittin groups were smaller than those of NS group.As observed by light and electron microscope,there was necrosis in tumor tissues in different degree in treatment groups,and no necrosis in NS group.No significant difference in peripheral blood cells and medullary karyotes of nude mice of different groups was found,and no significant morphological changes were observed in the myocardium,lung,spleen,liver,and brain under the light microscope.Conclusion：Melittin could significantly inhibit the growth of osteogenic sarcoma tibia xenograft in BALB/C nude mice in a dose-dependent manner.Melittin had no any toxic and side effectss.