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骨髓间充质干细胞与银杏叶提取物(EGb761)联合治疗对实验性自身免疫性脑脊髓炎大鼠模型的增强神经保护作用

Enhanced Neuroprotective Effects of Combination Therapy with Bone Marrow-Derived Mesenchymal Stem Cells and Ginkgo biloba Extract (EGb761) in a Rat Model of Experimental Autoimmune Encephalomyelitis.

作者信息

Hao Fei, Li Aiping, Yu Huan, Liu Meichen, Wang Yachen, Liu Jing, Liang Zhanhua

机构信息

Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, PR China.

出版信息

Neuroimmunomodulation. 2016;23(1):41-57. doi: 10.1159/000437429. Epub 2015 Oct 8.

DOI:10.1159/000437429
PMID:26468875
Abstract

OBJECTIVES

We investigated whether Ginkgo biloba extract (EGb761) can provide neuroprotective effects and enhance the efficacy of bone marrow-derived mesenchymal stem cells (BMSCs) in a rat model of experimental autoimmune encephalomyelitis (EAE).

METHODS

We examined the synergistic action of BMSCs combined with EGb761 treatment in EAE rats. The immunized rats received an intravenous injection of BMSCs or intraperitoneal administration of EGb761 or both on the day of the onset of clinical symptoms and for the following 21 days. Clinical severity scores were recorded daily and histopathological examination of the spinal cord and cytokine concentrations in the serum were studied on days 14 and 31 postimmunization.

RESULTS

Our results showed that combined treatment with BMSCs and EGb761 further decreased the disease severity, maximal clinical score and number of infiltrated mononuclear cells, especially CD3-positive T cells. We observed that the demyelination score and the density of axonal loss in the spinal cord were significantly reduced in mice receiving the combination therapy. The serum concentrations of the phosphorylated neurofilament heavy chain, tumor necrosis factor-α and interferon-γ were reduced in the combination-treatment group.

CONCLUSION

Our results suggest that combined treatment with BMSCs and EGb761 have a synergistic effect in rats with EAE by inhibiting the secretion of proinflammatory cytokines, demyelination and protecting axons and neurons.

摘要

目的

我们研究了银杏叶提取物(EGb761)是否能在实验性自身免疫性脑脊髓炎(EAE)大鼠模型中提供神经保护作用并增强骨髓间充质干细胞(BMSC)的疗效。

方法

我们检测了BMSC与EGb761联合治疗在EAE大鼠中的协同作用。在临床症状出现当天及随后21天,对免疫大鼠静脉注射BMSC或腹腔注射EGb761或两者同时注射。每天记录临床严重程度评分,并在免疫后第14天和第31天对脊髓进行组织病理学检查并研究血清细胞因子浓度。

结果

我们的结果表明,BMSC与EGb761联合治疗进一步降低了疾病严重程度、最大临床评分和浸润单核细胞数量,尤其是CD3阳性T细胞。我们观察到,接受联合治疗的小鼠脊髓脱髓鞘评分和轴突损失密度显著降低。联合治疗组血清中磷酸化神经丝重链、肿瘤坏死因子-α和干扰素-γ浓度降低。

结论

我们的结果表明,BMSC与EGb761联合治疗通过抑制促炎细胞因子分泌、脱髓鞘以及保护轴突和神经元,对EAE大鼠具有协同作用。

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