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逆转录病毒介导神经营养因子-3基因转染嗅鞘细胞移植对自身免疫性脑脊髓炎的治疗作用 被引量:1

The treatment of offactory ensheathing ceHs-neurotrophin-3 gene engineering cell transplantation on experimental allergic encephalomyelitis
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摘要 目的研究逆转录病毒介导神经营养因子-3(neurotrophin-3,NT-3)基因转染的嗅鞘细胞(olfactory ensheathing cells,OECs),即OECs—NT-3基因工程细胞对自身免疫性脑脊髓炎(experimental allergic encephalomyelitis,EAE)的髓鞘及轴突的修复作用并探讨其机制。方法构建OECs—NT-3基因工程细胞,将其移植入EAE大鼠的侧脑室,观察其在体内的迁徙、分布特点、NT-3 mRNA转录水平,从组织病理变化、神经突触素灰度值、功能学评分等方面对髓鞘及轴突修复进行评价。结果(1)OECs—NT-3细胞在EAE体内存活,可广泛迁徙至病灶远端且至少可以持续存活4周;(2)转基因组NT-3mRNA转录水平为(212.3±16.1)×10^-2,明显高于OECs组[(1.23±0.13)×10^-2]及对照组[(1,98±0.19)×10^-2],差异有统计学意义(t=-31.161、-31.928,P〈0.01);(3)转基因组髓鞘完整,炎性病灶数少于OECs移植组及对照组,差异有统计学意义(t=11.388~22.728,P〈0.01);(4)转基因组突触素灰度值(80.02±7.10)明显高于OECs移植组(53.65±8.90)及对照组(39.08±7.30),差异有统计学意义(P〈0.01)。结论OECs—NT-3细胞在EAE大鼠体内稳定、高效表达NT-3,可促进EAE的髓鞘修复及轴突再生。 Objective To explore the repair mechanism of olfactory ensheathing ceils (OECs)- neurotrophin-3 (NT-3) gene engineering cell on neuron myeline and axon of experimental allergic encephalomyelitis (EAE). Methods OECs-NT-3 gene engineering cell, constructed by neurotrophin-3 transinfecting OECs inducted by retrovirus, was transplanted into lateral ventricle. The migration and distribution were observed and compared with control group and OECs transplantation group. Then myeline repair and axon regeneration were evaluated in the aspects of function score, morphological structure, SYN grey level. Results (1) OECs-NT-3 could survive, diffuse, migrate with axons, spread in the focus diffusely on the 28th day after transplantation. (2) OECs-NT-3 survived and migrated to the transcription level of NT-3 mRNA in transgene group, being (212. 3 ±16. 1 ) ×10^-2, significantly higher than OECs group ((1.98 ±0. 19)×10^-2) and the contrast group ((1.23 ±0. 13) ×10^-2, t= -31. 161, -31.928, P 〈 0. 01 ). (3) The myeline of transgene group was kept complete and the number of inflamatory focus was lower than those of other groups (t = 11. 388-22. 728, P 〈0.01 ). (4) The SYN grey level of transgene group was obviously higher (P 〈 0. 01 ). Conclusion OECs-NT-3 cell expresses NT-3 in EAE stably and effectively, which contributes to the repair of myeline and the regeneration of axon.
出处 《中华神经科杂志》 CAS CSCD 北大核心 2009年第1期34-37,共4页 Chinese Journal of Neurology
基金 国家自然科学基金资助项目(30770751) 山东省卫生厅青年基金项目(2007QZ002)
关键词 脑脊髓炎 自身免疫性 实验性 基因疗法 神经营养因子-3 基因转移技术 Encephalomyelitis, autoimmune, experimental Gene therapy Neurotrophic 3 Gene transfer techniques
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参考文献8

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