摘要
目的 探讨分子模拟疫苗对C6/SD大鼠胶质瘤模型治疗的效果与机制.方法 混合同种异基因型的9L胶质瘤细胞及其裂解物与同基因型的C6胶质瘤细胞裂解物配制分子模拟疫苗.以C6胶质瘤细胞植入SD大鼠颅内建立动物模型.39只大鼠按随机数字表法随机分为10万治疗组、20万治疗组、对照组（每组13只）.造模后8d皮下接种疫苗,观察生存时间.造模后7、14、21、28、35、70 d行MRI检查并计算肿瘤体积.造模后20 d,每组随机选取3只大鼠行HE染色和免疫组织化学染色检测,分析Fascin、HS1、MMP-2、Podoplanin、CD4、CD8的表达.结果 10万治疗组和20万治疗组的生存时间（分别为29.0 d、47.5d）较对照组延长（18.5 d）,差异有统计学意义（P＜0.05）,而2个治疗组的生存时间差异无统计学意义（P＞0.05）;2个治疗组的肿瘤体积呈先增大,再逐渐缩小.在造模后的14 d和21 d,2个治疗组肿瘤的平均体积[14 d为（220.68 ± 45.92） mm3、（164.98 ±45.36）mm3;21 d为（426.48±39.69） mm3、（376.23±43.89） mm3]均小于对照组[14 d为（265.30±40.57） mm3、21 d为（515.64±15.28）mm3],差异均有统计学意义（均P ＜0.05）;2个治疗组的肿瘤体积均数之间差异无统计学意义（P＞0.05）;造模后20d,治疗组胶质瘤细胞密度低于对照组;治疗组Fascin、HS1、MMP-2、Podoplanin的表达低于对照组;治疗组CD4、CD8的表达高于对照组.结论 分子模拟疫苗能诱导荷瘤大鼠产生针对颅内胶质瘤的免疫反应,从而减小肿瘤体积,降低肿瘤侵袭力,延长大鼠的生存时间.
Objective To explore the therapeutic effect and mechanism of molecular mimicry-based vaccine in C6/SD rat model.Methods Mixed vaccines were prepared containing allogeneic 9L cells and cell lysates and syngeneic C6 cell lysates.C6 glioma cells were implanted into SD rats to establish the animal model.A total of 39 rats were randomly divided into 100,000 treatment group,200,000 treatment group and control group.Subcutaneous vaccination were performed at 8 d post modeling and the survival time of rats was observed.MRI examination was taken at 7,14,21,28,35,70 d and the tumor volumes were measured.At 20 d,3 rats in each group were randomly selected for HE staining and immunohistochemical staining,and expressions of Fascin,HS1,MMP-2,Podoplanin,CD8 and CD4 were assessed.Results The survival time in the 100,000 and 200,000 treatment groups （29.0 d and 47.5 d,respectively） was longer than that in the control group （18.5 d） （P 〈 0.05） and there was no significant difference between the 2 treatment groups （P 〉 0.05）.The tumor volume in treatment group first increased and then gradually decreased.At 14 d and 21 d,the mean volumes of tumor in 100,000 and 200,000 treatment groups [14 d：（220.68 ± 45.92） mm3,（164.98± 45.36） mm3,respectively;21 d：（426.48 ± 39.69） mm3,（376.23 ± 43.89） mm3,respectively] were less than that in the control group [14 d：（265.30 ±40.57） mm3;21 d：（515.64 ± 15.28） mm3] （all P 〈0.05）.There was no significant difference between 2 treatment groups （P 〉 0.05）.At 20 d,the glioma cell density in the treatment groups was lower than that in the control group.The expression levels of Fascin,HS1,MMP-2 and Podoplanin in the treatment group were lower than that in the control group,while the expressions of CD4 and CD8 in treatment groups were higher than those in the control group.Conclusion The molecular mimicry-based vaccine could induce immune response to intracranial glioma in tumor bearing rats,thereby reducing tumor volume and invasiveness and prolonging the survival time of rats.
作者
何海平
彭里磊
曾山
陈礼刚
He Haiping;Peng Lilei;Zeng Shan;Chen Ligang(Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Chin)
出处
《中华神经外科杂志》
CSCD
北大核心
2018年第4期411-416,共6页
Chinese Journal of Neurosurgery
基金
四川省科技厅重点科技自筹项目（2013SZZ002）
四川省科学技术厅-泸州市人民政府-泸州医学院联合科研专项资金（LZ-LY-9）
四川省卫生和计划生育委员会普及应用项目（16PJ557）
