新型重组免疫毒素DT390-mRantes治疗小鼠EAE的初步研究  

Primary study of the recombinant immunotoxin DT390-mRantes in EAE therapy

作　　者：贾怡[1] 李虹[1] 陈文捷[1] 吕梅励[1] 李明远[1] 蒋忠华[1] 张林[1] 

机构地区：[1]四川大学基础医学与法医学院物证教研室

出　　处：《细胞与分子免疫学杂志》2007年第3期236-239,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家高技术研究发展计划(863)资助项目(2002AA214101);国家自然基金委创新研究群体基金项目(30221001);四川省应用基础项目资助(04JY029-002)

摘　　要：目的:构建一种含有重组免疫毒素DT390-mRantes(白喉杆菌外毒素390片段-活化T细胞表达与分泌调节因子)的真核表达质粒,并用于治疗小鼠实验性自身免疫性脑脊髓炎(EAE)。方法:利用自提的MBP诱导C57BL/6小鼠产生EAE,将mRantes导入含有DT390的真核表达质粒SRα中,经阳离子纳米脂质体包被后,治疗小鼠EAE,同时对其临床症状、脑部病理改变、外周血相关细胞因子及T/B细胞比例进行检测,了解该重组免疫毒素的治疗效果。结果:成功构建真核表达质粒DT390-mRantes-SRα,治疗组小鼠临床症状减轻,脑部特异性淋巴细胞浸润减少,外周T细胞相关细胞因子表达降低,T/B细胞比例降低。结论:新型重组免疫毒素DT390-mRantes治疗小鼠EAE有较为明显的效果,为治疗人的多发性硬化(MS)提供有益的借鉴。AIM： To construct a novel eukaryotic expression plasmid including the recombinant immunotoxin DT390-mRantes and treat experimental autoimmune encephalomyelitis （EAE） in mice. METHODS. EAE in C57BL/6 mice were induced by the extracted MBP. The mRantes fragment was inserted into the eukaryotic expression plasmid SRα containing DT390. Then cationic liposome-embedded plasmid DNA was injected into the muscles of the hind-limbs in mice. The effect of DT390-mRantes was evaluated by observing clinical symptoms, pathological changes of brain, relative cytokine of peripheral blood, and the proportion of T cells and B cells. RESULTS： The recombinant immunotoxin DT390-mRantes was successfully constructed. Compared the mice in treated group with those in untreated group the clinical symptoms of EAE were allevi- ated, the infiltration of inflammatory cells were decreased, the IFN-y level was fallen, and the ratio of T/B cells was decreased. CONCLUSION： The recombinant immunotoxin DT390-mRantes has distinct effects on EAE in mice, which may be used for beneficial reference to the therapy of MS.

关 键 词：实验性变态性脑脊髓炎 DT390 mRantes 重组免疫毒素 

分 类 号：R392.11[医药卫生—免疫学]