靶向治疗脑胶质母细胞瘤干细胞研究小鼠模型的建立  

Establishment of mice models of targeted therapy for glioblastoma stem cells

作　　者：杨帅 陈蕊[2] 王蔚[3] 王伟民 

机构地区：[1]广军州区广州总医院神经外科,广州510010 [2]广州军区广州总医院老年重症医学科,广州510010 [3]广州军区广州总医院病理科,广州510010

出　　处：《中华神经医学杂志》2017年第3期233-237,共5页Chinese Journal of Neuromedicine

基　　金：广东省科技计划项目（20128031800186）

摘　　要：目的通过置入微量渗透压泵，建立符合靶向治疗脑胶质母细胞瘤干细胞研究需要的在体模型．为靶向抑制剂的在体研究提供实验基础。方法近交系雌性SCID小鼠10只，于右侧室管膜下区立体定向接种5μL人脑胶质母细胞瘤干细胞株（ESQ RT＋TMZ）（2×10^4个／μL）并安装可以持续输注的微量渗透压泵。观察小鼠的生存状态和濒死期症状出现的时间。处死小鼠，取出全脑大体标本观察并测定肿瘤直径，HE染色观察肿瘤的病理特征。结果10只小鼠全部存活，能够耐受2次连续手术操作，在大体标本及组织学检查中均发现肿瘤形成，致瘤率100％，肿瘤最大横截面直径达（5．10±0．52）mm，且成瘤速度和形态均一、状况稳定，平均生存期（48．4±4．9）d，具备可重复性。HE染色显示组织病理学特点接近人脑胶质母细胞瘤病理特征。结论采用微量渗透压泵进行精准输注的方式成功建立符合靶向治疗脑胶质母细胞瘤干细胞研究需要的在体模型，为靶向抑制剂抗肿瘤的在体实验提供了基础。Objective To establish models of targeted therapy for glioblastoma stem cell xenografs growth in mice by using micro-osmotic Pumps to provide experimental foundations for the targeted inhibitors in treating glioblastoma in vivo. Methods Human glioblastoma stem cells of 2×10^4cells/μL were inoculated into 10 inbred strain female SCID mice by using stereotactic technique （right subependymal zone）; micro-osmotic pumps by which targeted inhibitors could be infused into aimed regions were immediately installed in the mice. Evaluation of whether mice could tolerate this surgery was performed after the operation. Survival data and time of agonal stage were observed and recorded after the operation. Then, the xenograft tumors in animal models were evaluated. In addition, the gross tumor size was measured and HE staining was performed to assess the pathological features. Results All of the 10 mice models accepted glioblastoma stem cells and micro-osmotic pumps survived and these mice could tolerate two consecutive surgical procedures. Tumorigenic rate was 100% and the size of the isolated tumors was very similar with each other, with the largest cross sectional diameter reaching （5.10±0.52） mm. Besides, the survival time of these mice models was （48.4±4.9） d. HE staining results showed that the histopathologic features were close to the human glioblastoma pathological features. Conclusions Mice models of glioblastoma stem cells are successfully established by using micro-osmotic pumps to infuse targeted inhibitors. The pathological observations and data may provide promising references for the next targeted inhibitors in treating tumors in vivo.

关 键 词：靶向治疗 动物模型 胶质母细胞瘤干细胞 微量渗透压泵 

分 类 号：R-332[医药卫生] R739.41