SPK1基因转染的UCMSC移植对EAE小鼠的治疗作用

发布时间：2018-01-30 14:08

本文关键词： 多发性硬化脐带间充质干细胞鞘氨醇激酶实验性自身免疫性脑脊髓炎小鼠　出处：《郑州大学学报(医学版)》2017年02期 　论文类型：期刊论文

【摘要】：目的:观察鞘氨醇激酶1(SPK1)基因转染的脐带间充质干细胞(UCMSC)移植对实验性自身免疫性脑脊髓炎(EAE)小鼠的疗效。方法:将C57BL/6小鼠分为对照组(12只)、EAE组、UCMSC组和UCMSC-SPK1组;后3组进行免疫诱导以制备EAE模型,每组11只。以第一次注射抗原当日为第0天,UCMSC组和UCMSC-SPK1组小鼠分别在免疫后第14、21、28天通过尾静脉注射UCMSC和UCMSC-SPK1,对照组和EAE组注射同等体积的生理盐水。每日采用双盲法进行小鼠神经功能缺损评分;第33天,ELISA法检测外周血IFN-γ、TNF-α、IL-17和L-4水平,分别采用HE和Fast-blue(LFB)染色观察并进行脊髓炎性细胞浸润评分、脱髓鞘评分,免疫组化法检测脊髓GFAP和MBP的表达,流式细胞术检测脾脏中调节性T细胞和NK细胞比例。结果:与EAE组比较,UCMSC-SPK1组和UCMSC组小鼠神经功能缺损评分、脊髓炎性细胞浸润评分和脱髓鞘评分降低,脾脏调节性T细胞比例升高、NK细胞比例降低;UCMSC-SPK1组变化更为显著(P0.05);UCMSC-SPK1组脊髓GFAP表达较EAE组下降,MBP表达增强(P0.05),外周血IFN-γ、TNF-α、IL-17水平降低,IL-4水平升高(P0.05)。结论:UCMSC-SPK1移植能较UCMSC更为显著地修复EAE小鼠神经功能损伤。
[Abstract]:Objective: to observe the effect of UCM SCC transplantation on experimental autoimmune encephalomyelitis (EAE) with sphingosine kinase 1 (SPK1) gene transfected umbilical cord mesenchymal stem cells (UCM SCC). Methods: C57BL / 6 mice were divided into control group (n = 12). EAE group, UCMSC group and UCMSC-SPK1 group; The last three groups were immunized to make EAE model with 11 mice in each group. The mice in UCMSC group and UCMSC-SPK1 group were immunized at the 14th day after immunization. UCMSC and UCMSC-SPK1 were injected through tail vein for 28 days, and the same volume of normal saline was injected into control group and EAE group. The levels of IL-17 and L-4 in peripheral blood of IFN- 纬 -TNF- 伪 were detected by Elisa on the 33rd day. The expression of GFAP and MBP in spinal cord were detected by HE and Fast-blueblueLFB staining respectively. The spinal cord inflammatory cell infiltration score demyelination score and immunohistochemical method were used to detect the expression of GFAP and MBP in spinal cord. Results: compared with EAE group, UCMSC-SPK1 group and UCMSC group were compared with UCMSC-SPK1 group and UCMSC group. The scores of inflammatory cell infiltration and demyelination of the spinal cord decreased, while the proportion of regulatory T cells in the spleen increased and the proportion of NK cells decreased. The changes in UCMSC-SPK1 group were more significant than those in P0.05 group. The expression of GFAP in spinal cord in UCMSC-SPK1 group was higher than that in EAE group, and the level of IL-17 in peripheral blood was lower than that in EAE group. Conclusion the transplantation of IL-4 can repair the nerve function injury of EAE mice more significantly than that of UCMSC. Conclusion\% UCMSC-SPK1 transplantation is more effective than UCMSC in repairing nerve function injury in EAE mice.
【作者单位】：郑州大学第二附属医院神经内科;中国人民解放军第148医院神经内科;首都医科大学三博脑科医院神经内科;海军总医院海战伤研究所;军事医学科学院放射与辐射医学研究所;
【基金】：国家自然科学基金青年基金项目81201760
【分类号】：R744.51
【正文快照】： 1)郑州大学第二附属医院神经内科郑州450014 2)中国人民解放军第148医院神经内科山东淄博255300 3)首都医科大学三博脑科医院神经内科北京100093 4)海军总医院海战伤研究所北京100037 5)军事医学科学院放射与辐射医学研究所北京100850#通信作者:王运良,男,1964年11月生,博士,

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