骨髓基质干细胞治疗实验性自身免疫性神经炎的研究_医学论文.docVIP

骨髓基质干细胞治疗实验性自身免疫性神经炎的研究_医学论文 骨髓基质干细胞治疗实验性自身免疫性神经炎的研究_医学论文 作者：徐欣, 孙博, 穆莉莉, 王广友, 金连弘, 李呼伦 【关键词】 实验性自身免疫性神经炎,骨髓基质干细胞,Th1/Th2型细胞,细胞因子 　　Study on therapy of experimental autoimmune neuritis by bone marrow stromal cells 　　[Abstract] AIM: To investigate the therapeutic effect of bone marrow stromal cells (BMSCs) transplantation on experimental autoimmune neuritis (EAN) and study the possible mechanism. METHODS: EAN model was established by immunizing Lewis rats with P0180199 peptide and complete Freund’s adjuvant (CFA). In the therapy group, BMSCs (2×106 cells/rat) were marked with fluorochrome PKH26 and injected into the rats’ caudal vein 10 d after immunization. The therapeutic effect of BMSC transplantation on EAN rats was investigated by clinical assessment, immunohistochemical staining, and ELISA, respectively. RESULTS: The injected BMSCs could migrate to the demyelinated nerve tissues, and the demyelination and inflammatory infiltration was relieved. The infiltration of CD4+ and CD8+ T cells and the sera level of IFNγ and TNFα were decreased significantly（0.05）, whereas IL4 level in the supernatant of cultured lymphocytes was increased （0.05）. CONCLUSION: Certain therapeutic effect of BMSC transplantation on EAN was observed. BMSCs could reverse the disbalance of Th1/Th2 cells by regulating the cytokine expression and could inhibit the activation and proliferation of T cells. 　　[Keywords]EAN BMSC Th1/Th2 cell cytokine 　　[摘 要] 目的: 探讨骨髓基质干细胞（BMSC）移植治疗实验性自身免疫性神经炎（experimental autoimmune neuritis, EAN）的疗效以及相应的作用机制。方法: 用P0180199多肽与弗氏完全佐剂的混合液免疫Lewis大鼠, 建立EAN动物模型。治疗组在免疫后第10天, 尾静脉回输荧光染料PKH26标记的BMSC（2×106个细胞/只）, 通过临床评估、 免疫组化及ELISA等方法, 研究了BMSC对EAN的治疗作用。结果: 回输的BMSC能向脱髓鞘神经组织周围迁移, 减轻脱髓鞘的病理改变和炎性细胞浸润。与对照组比较,治疗组CD4+和CD8+ T细胞的浸润显著减少（0.05）, 血清中IFNγ和TNFα的水平明显降低（0.05）, 培养上清中IL4的水平显著增加（0.05）。结论: BMSC静脉移植治疗EAN有一定的疗效。BMSC通过调节细胞因子的表达逆转Th1/Th2型细胞之间的失衡而发挥治疗作用, 并能够抑制T细胞活化增殖。 　　[关键词]实验性自身免疫性神经炎 骨髓基质干细胞 Th1/Th2型细胞 细胞因子 　　格林巴利综合征（GuillainBarre syndrome, GBS）, 是临床上最常见的急性瘫痪性疾病, 具有较高的致残率和病死率[1], 目