Fasudil联合骨髓源神经干细胞对EAE小鼠的神经保护作用

发布时间：2018-07-23 11:30

【摘要】：目的:探讨Rho激酶抑制剂法舒地尔(fasudil)联合骨髓源神经干细胞(bone marrow-derived neural stem cells,BM-NSCs)对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)小鼠的神经保护作用。方法:32只雌性C57BL/6小鼠(8~10周龄),用髓鞘少突胶质细胞糖蛋白35-55(MOG35-55)免疫,制备EAE,随机分为对照(dd H_2O)组、fasudil组、BM-NSCs组和fasudil+BM-NSCs组,并分别给予相应处理。免疫后检测小鼠临床症状和相关神经营养因子的表达,Image-Pro Plus 6.0软件进行阳性细胞计数,Graph Pad Prism 5软件统计分析。结果:与dd H_2O组比较,fasudil+BM-NSCs处理组明显延迟小鼠的平均起病时间,降低最高临床评分,并缓解EAE小鼠的临床症状;fasudil组、BM-NSCs组和fasudil+BM-NSCs组中脑源性神经营养因子、胶质细胞源性神经营养因子、神经生长因子、神经营养因子3和睫状神经营养因子阳性细胞数均有不同程度的增加,其中,fasudil+BM-NSCs组上述神经营养因子的表达明显多于dd H_2O组、fasudil组和BM-NSCs组(P0.01)。结论:Fasudil联合BM-NSCs通过协同和叠加效应促进神经营养因子表达,改善中枢神经系统微环境,发挥神经保护作用,从而缓解EAE的临床症状。
[Abstract]:Aim: to investigate the neuroprotective effects of Rho kinase inhibitor fasudil (fasudil) combined with bone marrow-derived neural stem cells BM-NSCs on experimental autoimmune encephalomyelitis (experimental autoimmune) mice. Methods Thirty-two female C57BL/6 mice (810 weeks old) were immunized with oligodendrocyte glycoprotein 35-55 (MOG35-55). The mice were randomly divided into two groups: control group (d / H _ 2O) group, fasudil group (n = 10) and fasudil BM-NSCs group (n = 10). After immunization, the clinical symptoms and the expression of related neurotrophic factors in mice were detected by Image-Pro Plus 6.0 software. The positive cells were counted and analyzed by Graph Pad Prism5 software. Results: compared with the d H2O group, the treatment group of fasudil BM-NSCs significantly delayed the onset time, decreased the highest clinical score, and alleviated the clinical symptoms of BM-NSCs and fasudil BM-NSCs in BM-NSCs group and fasudil BM-NSCs group. The number of glial cell derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophic factor 3 (NGF) and ciliary neurotrophic factor (ciliary neurotrophic factor) positive cells increased in varying degrees. The expression of these neurotrophic factors in the fasudil BM-NSCs group was significantly higher than that in the d d H 2O group, fasudil group and BM-NSCs group (P0.01). Conclusion the expression of neurotrophic factor can be promoted by the synergistic and superimposed effect of BM-NSCs, the microenvironment of central nervous system can be improved and the neuroprotective effect can be brought into play so as to alleviate the clinical symptoms of EAE.
【作者单位】：山西大同大学脑科学研究所;山西中医学院神经生物学研究中心;复旦大学华山医院神经病学研究所;托马斯.杰弗逊大学神经学系;
【基金】：国家自然科学基金资助项目(No.81501198、No.81272163) 山西大同大学青年科研基金资助项目(No.2013Q11) 山西省回国留学人员重点科研资助项目(No.2014-重点7) 山西中医学院“2011”培育计划项目(No.2011PY-1)
【分类号】：R744.51

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