新型重组免疫毒素DT390_医学论文.docVIP

新型重组免疫毒素DT390_医学论文 新型重组免疫毒素DT390_医学论文 作者：贾怡, 李虹, 陈文捷, 吕梅励, 李明远, 蒋忠华, 张林 【关键词】 实验性变态性脑脊髓炎,DT390,mRantes,重组免疫毒素 　　Primary study of the recombinant immunotoxin DT390mRantes in EAE therapy 　　[Abstract] AIM: To construct a novel eukaryotic expression plasmid including the recombinant immunotoxin DT390mRantes 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 liposomeembedded plasmid DNA was injected into the muscles of the hindlimbs in mice. The effect of DT390mRantes 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 DT390mRantes was successfully constructed. Compared the mice in treated group with those in untreated group the clinical symptoms of EAE were alleviated, the infiltration of inflammatory cells were decreased, the IFNγ level was fallen, and the ratio of T/B cells was decreased. CONCLUSION: The recombinant immunotoxin DT390mRantes has distinct effects on EAE in mice, which may be used for beneficial reference to the therapy of MS. 　　[Keywords]experimental autoimmune encephalomyelitis (EAE) DT390 mRantes recombinant immunotoxin 　　[摘 要] 目的: 构建一种含有重组免疫毒素DT390mRantes（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DT390mRantesSRα, 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DT390mRantes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。 　　[关键词]实验性变态性脑脊髓炎 DT390 mRantes 重组免疫毒素 　　人的多发性硬化（multiple sclerosis, MS）是一种难以治愈的以中枢神经系统脱髓鞘病变为主要特征的自身免疫性疾病。实验性动物自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis, EAE）, 又称为实验性变态反应性脑脊髓炎（experimental allergic encephalomyelitis）与MS