GM-CSF与BZLF1融合基因重组BCG抗肿瘤研究  

Anti-tumor research on rBCG with a fusion gene consisting of GM-CSF and BZLF1

作　　者：薛庆节[1,2] 杨春青 胡文洁[1] 吕厚东[1] 陈廷[1] 司传平[1] 李士根[1] 

机构地区：[1]济宁医学院基础学院 [2]山东省神经生物学重点实验室,山东济宁272067

出　　处：《中国病原生物学杂志》2015年第7期603-605,共3页Journal of Pathogen Biology

基　　金：山东省高等学校科技计划项目(No.J12LK56);山东省自然科学基金项目(No.ZR2012HM037);教育部留学回国人员科研启动基金资助项目(No.20101174)

摘　　要：目的对已融合的人粒细胞-巨噬细胞集落刺激因子基因(GM-CSF)与EB病毒即刻早期基因(BZLF1)进行抗肿瘤活性及免疫学研究。方法建立C57BL/6小鼠肿瘤模型,rBCG注射免疫后采用ELISA检测其特异性抗体,用乳酸脱氢酶法检测特异性CTL,HE染色检测肿瘤组织中的淋巴细胞浸润情况。并对各试验组小鼠成瘤时间、肿瘤大小进行分析,采用t检验方法对重组BCG抗肿瘤效果进行初步分析和评价。结果 rBCG免疫小鼠肿瘤成瘤时间延迟,最迟长达11.9d;肿瘤生长缓慢,生存时间显著延长,平均抑瘤率为82%;rBCG刺激小鼠产生特异性GM-CSF和BZLF1抗体,特异性CTL活性增强;当效靶比(E/T)为40∶1时,CTL杀伤率为(37.25士5.09)%;HE染色镜检肿瘤组织中淋巴细胞浸润。结论重组BCG免疫小鼠能诱导产生特异性体液免疫和细胞免疫,可抑制EB病毒阳性肿瘤细胞生长。Objective The antitumor activity and immunological mechanisms of rBCG including a fusion gene consisting of GM-CSF and BZLF1 were studied. Methods C57BL/6mice were used to create an animal model of EB virus-positive tumors.Antitumor activity was then analyzed in terms of how long tumors took to develop,survival time,and tumor size.Specific antibodies in mice stimulated with rBCG were detected with ELISA.A lactate dehydrogenase assay was used to detect mouse cellular immunity and HE staining of tumor tissue was used to assay lymphocyte infiltration in mouse tumors.Immunization with rBCG was also analyzed statistically. Results The time that tumors took to develop was delayed in mice immunized with rBCG.The longest delay was 11.9days.Tumor growth was slow and mice had a prolonged survival time.The average rate of tumor inhibition by rBCG was 82%.Mice immunized with rBCG produced specific IgG antibodies to GM-CSF and BZLF1.Specific CTL activity in mice was also examined.When the target ratio（E/T）was40：1,the killing rate of CTL was（37.25士5.09）%.Tumor tissue infiltration by lymphocytes was noted in microscopy after HE staining. Conclusion Humoral and cellular immune responses were produced in mice immunized with rBCG.rBCG had potent antitumor action.EB virus-positive tumors were significantly inhibited in mice.

关 键 词：粒细胞-巨噬细胞集落刺激因子基因 即刻早期基因 重组卡介苗 抗肿瘤 

分 类 号：R511[医药卫生—内科学]