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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。
OBJECTIVE: To construct a eukaryotic expression plasmid containing the recombinant immunotoxin DT390-mRantes (fragment of Exotericum of diphtheriae-390, activated T cell expression and secretion) and to treat mouse experimental autoimmune encephalomyelitis (EAE ). Methods: EAE was induced in C57BL / 6 mice by using self-raised MBP. The mRantes were introduced into the eukaryotic expression plasmid SRα containing DT390. After being coated with cationic liposomes, the mice were treated with EAE. The clinical symptoms, Brain pathological changes, peripheral blood related cytokines and T / B cell ratio to detect the therapeutic effect of the recombinant immunotoxin. Results: The eukaryotic expression plasmid DT390-mRantes-SRα was successfully constructed. The clinical symptoms, alleviation of brain-specific lymphocyte infiltration, the decrease of peripheral T cell-related cytokines and the decrease of T / B ratio were observed in the treatment group. CONCLUSION: The new recombinant immunotoxin DT390-mRantes has a significant effect on the treatment of EAE in mice and provides a useful reference for the treatment of multiple sclerosis (MS) in humans.