《中国康复理论与实践》 ›› 2009, Vol. 15 ›› Issue (08): 742-744.

• 基础研究 • 上一篇    下一篇

大鼠C6胶质瘤模型构建及生长特性的研究

王建交1;李青松1;詹奇1;郑永日1;刘福生2   

  1. 1. 哈尔滨医科大学附属第二医院神经外科,黑龙江哈尔滨市 150086;2. 北京市神经外科研究所首都医科大学附属北京天坛医院神经外科,北京市 100050
  • 收稿日期:2009-06-11 出版日期:2009-08-01 发布日期:2009-08-01
  • 通讯作者: 刘福生

Natural Growth Characteristics in C6 Glioma Model

WANG Jian-jiao,LI Qing-song,ZHAN Qi,et al   

  1. Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
  • Received:2009-06-11 Published:2009-08-01 Online:2009-08-01

摘要: 目的 建立Wistar大鼠C6胶质瘤模型,研究C6脑胶质瘤的发生、发展过程,细胞侵袭情况,肿瘤细胞及血管特性,肿瘤自发消退现象,模型最佳应用时间段及应用范围。方法 Wistar大鼠各50只,其中9只用于对照。将C6胶质瘤细胞悬液和DMEM培养基立体定向接种于大鼠的右侧尾状核,分别于接种后3,7,14,21,28,35,50 d进行增强MRI扫描及病理切片HE染色,MMP-2,CD31免疫组化染色。同时观察荷瘤鼠的生物学行为。结果 肿瘤模型于接种后7 d可在MRI上见到肿瘤生长,病理切片可见肿瘤细胞沿神经纤维向周边侵袭,成出芽状生长,14~28 d为快速增长期,免疫组化染色显示基质金属蛋白酶MMP-2及新生血管CD31成强阳性表达,肿瘤细胞聚集,血脑屏障严重破坏,并可沿胼胝体向对侧生长。大部分荷瘤鼠死于30 d内,但有2只28 d后出现肿瘤自发消退现象,病理切片可见大量炎细胞浸润,肿瘤内部出现软化灶。结论 大鼠C6胶质瘤模型的生长过程,病理性质与人脑间变,胶质母细胞瘤具有相似性,生长稳定。尽管部分荷瘤鼠出现肿瘤自发消退现象,但此模型仍适合大部分抗胶质瘤药物或基因治疗等的临床前期研究。试验研究最佳时间窗为14~28 d。

关键词: C6胶质瘤, 自然生长规律

Abstract: Objective To establish C6 glioma model in rat brain and to study its biological behavior(such as the incidence of tumor development, the process of cell invasion pathological characteristics of C6 and neoangiogenesis, the spontaneous regression of experimental gliomas and the best experimental time window).Methods C6 tumor cells and DMEM were implanted into the right caudate of 50 male Wistar rats. 9 rats implanted DMEM is the control group. The animals were examined by MRI and pathological staining at postoperative day (POD) 3, 7, 14, 21,28, 35, and 50. Matrix metalloproteinases-2 (MMP-2) and CD31 immunohistochemistry staining were used to study the histopathological features of the developed tumor. Methodology, physical findings and biological behavior were also discussed. Results 45 Wistar rats survived after surgery and tolerated MRI procedures well. On POD 7, there was a focal signal at the implantation site. The C6 cells sprout to the surroundings along the nerve fiber. During the day 14~28, the tumor exhibited a marked increase in size with focal mass effect, and immunohistochemical-staining shows MMP-2 and CD31 is overexpression; C6 cells were aggregated and blood brain barrier were destroyed greatly. Most of the tumor bearing rats died within 30 days. But, C6 cells in the two rats retrogress spontaneously after more leucocytes rounded 28 days. HE staining shows tumors.Conclusion The characteristics of rat C6 brain tumor model mimicked the human tumor with respect to its development, progression, and invasion. Although, part of C6 tumor spontaneously regressed, it is a useful animal model of glioblastoma for pre-clinical evaluation of various therapeutic strategies for the management of glioblastoma. The best experimental time window is 14 to 28 days.

Key words: C6 cells, law of natural growth