神经母细胞瘤肾上腺原位移植瘤动物模型的建立  

Establishment of an orthotopic xenografted animal model of neuroblastoma

作　　者：刘波[1,2] 苗佳宁 张斯萌[1] 李志杰 LIU Bo;MIAO Jianing;ZHANG Simeng;LI Zhijie(Medical Research Center,Shengjing Hospital of China Medical University,Shenyang 110004,China;Liaoning Key Laboratory of Research and Application of Animal Models for Environmental and Metabolic Diseases,Shenyang 110004)

机构地区：[1]中国医科大学附属盛京医院实验研究中心,沈阳110004 [2]辽宁省环境与代谢疾病动物模型研究与应用重点实验室,沈阳110004

出　　处：《中国比较医学杂志》2021年第12期1-6,共6页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(81472359);辽宁省科技厅重点研发指导计划(2019JH8/10300024)。

摘　　要：目的建立神经母细胞瘤肾上腺原位移植瘤动物模型,探讨其相对于传统皮下异位肿瘤移植模型的优势。方法体外培养人神经母细胞瘤细胞,开腹接种于SCID-Beige小鼠左侧肾上腺周围脂肪内,并分别在肿瘤细胞接种后第14、21、28天取瘤组织,与传统皮下异位移植的肿瘤比较成瘤率、肿瘤生长速度及组织病理等指标。结果注射相同数量肿瘤细胞后,原位移植鼠成瘤率在3个取材时间点均为100%,而皮下异位移植鼠成瘤率在3个取材时间点分别为33%、67%、78%,原位移植瘤成瘤率高于皮下异位移植瘤。接种肿瘤细胞的第14、21、28天原位移植瘤肿瘤体积分别为(116.21±78.82)、(245.32±97.31)、(3091.21±2042.39)mm^(3),皮下异位移植瘤肿瘤体积分别为(7.26±6.04)、(41.67±38.52)、(292.14±167.12)mm^(3),与皮下异位移植瘤相比,原位移植瘤生长速度更快、种瘤体积更大。肿瘤组织HE染色提示原位移植瘤肿瘤组织较皮下异位移植瘤肿瘤细胞密度更大。结论神经母细胞瘤肾上腺原位移植瘤动物模型技术可行,与皮下异位移植瘤模型相比具有成瘤率高、肿瘤生长速度快的优势;比皮下异位移植瘤更符合临床神经母细胞瘤生长位置,为深入研究神经母细胞瘤提供更准确和高效的动物模型。Objective To establish an orthotopic neuroblastoma xenograft model and evaluate it by comparison with the ectopic xenografted model.Methods SCID-Beige mice were used in the study.Neuroblastoma cells were implanted into the fat pad that surrounds the left adrenal gland to establish the orthotopic xenografted model or into the subcutaneous tissue of the right flank for the ectopic xenografted model.After the implantations,the tumor formation rate and size were evaluated at 7,14,and 21 days,and histopathological analysis was performed.Results After implantation of the same number of neuroblastoma cells,tumors formed in all orthotopic xenografted mice at the three time points,whereas 33%,67%,and 78%of ectopic xenografted mice had tumors,respectively.The orthotopic xenografted model showed a higher tumor formation rate than the ectopic xenografted model at the three time points.In the orthotopic xenografted model,the tumor volumes were(116.21±78.82),(245.32±97.31),and(3091.21±2042.39)mm^(3),whereas the tumor volumes were(7.26±6.04),(41.67±38.52),and(292.14±167.12)mm^(3)in the ectopic xenografted model at 14,21,and 28 days,respectively.Orthotopic xenografted tumors were larger than ectopic xenografted tumors at each time point.HE staining showed that the density of orthotopic xenografted tumor was higher than that of ectopic xenografted tumors.Conclusions The orthotopic xenografted model is applicable.Compared with the ectopic subcutaneous xenograft model,the orthotopic xenografted model had the advantages of higher tumor formation and growth rates.These data indicate that the orthotopic xenografted model is a better model for neuroblastoma research.

关 键 词：神经母细胞瘤 肾上腺原位移植瘤 动物模型 SCID-Beige鼠 

分 类 号：R-33[医药卫生]