网络出版日期: 2021-02-22
基金资助
山西省回国留学人员科研资助项目(HGKY2019089);大同市国际合作重点研发计划项目(2019123);中枢神经炎症变性疾病新药创制省市共建山西省重点实验室培育基地(201805D111009)
Therapeutic effects of the combination of fasudil and C-C chemokine receptor type 5-transducted mesenchymal stem cells on experimental autoimmune encephalomyelitis
Online published: 2021-02-22
Supported by
Funding Information] Research Project Supported by Shanxi Scholarship Council of China(HGKY2019089);International Key Research & Development Cooperation Plan of Datong(2019123);Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases(201805D111009)
目的·研究法舒地尔（fasudil）联合过表达趋化因子受体5（C-C chemokine receptor type 5，CCR5）的间充质干细胞（mesenchymal stem cells，MSCs）对实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis，EAE）的治疗效果。方法·小鼠经髓鞘少突胶质细胞糖蛋白第35~55位肽片段（myelin oligodendrocyte glycoprotein peptide fragment 35~55，MOG35-55）免疫后，随机分为EAE模型组（腹腔注射生理盐水）、fasudil干预组（腹腔注射fasudil）、CCR5-MSCs干预组（鼻腔给予CCR5-MSCs）、fasudil联合CCR5-MSCs干预组（鼻腔给予CCR5-MSCs，腹腔注射fasudil），每组8只。MOG35-55免疫后，每日记录EAE临床症状评分。于免疫后第28日处死小鼠，固蓝染色观察髓鞘完整性，免疫荧光染色分析脊髓组织中神经干细胞和少突胶质前体细胞的产生，Western blotting检测脊髓组织中神经营养因子的表达。结果·与其他3组相比，fasudil联合CCR5-MSCs干预组EAE临床症状评分降低（P=0.000，P=0.007，P=0.005），脱髓鞘减轻（P=0.000，P=0.009，P=0.008），脊髓组织中神经干细胞和少突胶质前体细胞的产生增多（均P=0.000），脑源性神经营养因子、胶质细胞源性神经营养因子、神经生长因子和神经营养因子3的表达增加（均P=0.000）。结论·Fasudil联合CCR5-MSCs对EAE的治疗效果较fasudil或CCR5-MSCs单独治疗更为显著，可能与其促进髓鞘再生和增加神经营养因子产生相关。
关键词： 法舒地尔; 趋化因子受体5; 间充质干细胞; 实验性自身免疫性脑脊髓炎
李艳花 , 闫亚平 , 刘晓琴 , 席国萍 , 宋国斌 , 肖保国 , 马存根 . 法舒地尔联合过表达趋化因子受体5的间充质干细胞对实验性自身免疫性脑脊髓炎的治疗作用[J]. 上海交通大学学报（医学版）, 2021 , 41(1) : 35 -41 . DOI: 10.3969/j.issn.1674-8115.2021.01.006
·To study the therapeutic effect of the combination of fasudil and C-C chemokine receptor type 5-transducted mesenchymal stem cells (CCR5-MSCs) on experimental autoimmune encephalomyelitis (EAE).
·The mice immunized with myelin oligodendrocyte glycoprotein peptide fragment 35-55 (MOG35-55) were randomly divided into EAE model group (intraperitoneal injection of normal saline), fasudil intervention group (intraperitoneal injection of fasudil), CCR5-MSCs intervention group (nasal administration of CCR5-MSCs), and fasudil combined with CCR5-MSCs intervention group (intranasal administration of CCR5-MSCs, intraperitoneal injection of fasudil), with 8 mice in each group. The clinical score of EAE mice were checked every day after MOG35-55 immunization. All mice were sacrificed on the 28th day after the first immunization. The myelin integrity was observed by luxol fast blue staining. The production of neural stem cells and oligodendrocyte precursor cells in spinal cord tissue was analyzed by immunofluorescence staining. The expressions of neurotrophic factors in spinal cord tissue were detected by Western blotting.
·Compared with the other three groups, the clinical score of EAE in the fasudil combined with CCR5-MSCs intervention group was lower (P=0.000, P=0.007, P=0.005), and the demyelination was reduced (P=0.000, P=0.009, P=0.008). The production of neural stem cells and oligodendrocyte precursor cells in spinal cord tissue was increased (all P=0.000), and the expression of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 increased (all P=0.000).
·Fasudil combined with CCR5-MSCs is more effective than fasudil or CCR5-MSCs in the treatment of EAE, which may be related to the induction of remyelination and the production of the neurotrophic factor.
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