| Rock抑制剂-Fasudil对EAE外周免疫的调节作用 |
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| 引用本文： | 尉杰忠,李艳花,刘春云,杨德兵,孟健,王力军,肖保国,马存根.Rock抑制剂-Fasudil对EAE外周免疫的调节作用[J].雁北师范学院学报,2013(1):50-54,69. |
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| 作者姓名： | 尉杰忠 李艳花 刘春云 杨德兵 孟健 王力军 肖保国 马存根 |
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| 作者单位： | [1]山西大同大学脑科学研究所,山西大同037009 [2]山西大同大学附属医院神经内科,山西大同037009 [3]复旦大学神经病学研究所,上海200040 |
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| 基金项目： | 国家自然科学基金2012年面上项目[81272163];国家自然科学基金2010年面上项目[81070957];山西大同大学青年科学研究基金项目[2010Q6] |
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| 摘 要： | 目的探讨Rock抑制剂Fasudil对实验性自身免疫性脑脊髓炎（EAE）发病起始环节的外周免疫调节机制。方法将雌性C57BL/6小鼠分为CFA组、EAE组和Fasudil组。Fasudil组动物免疫后第7 d腹腔给予Fasudi（l50mg/kg.d）,连续给药14 d。免疫后隔天观察各组小鼠临床评分和体质量变化。在免疫后28 d处死动物,取脊髓进行HE染色和髓鞘染色,制备脾脏单个核淋巴细胞（MNC）,测定细胞增殖和细胞因子IL-4,IL-10,IL-1β,IFN-γ的含量,流式细胞术观察CD4,CD25调节性T细胞的比例,部分脾脏组织和MNC涂片行免疫组化荧光染色观察Rock的表达。结果Fasudil在EAE外周免疫组织和细胞通过下调Rock的表达,抑制Rock的激活,明显改善EAE的临床症状评分（P〈0.05）;减轻EAE外周炎性细胞向中枢的浸润,缓解神经髓鞘的脱失;经Fasudil干预可以下调EAE外周特异性MOG35-55反应性T淋巴细胞增殖能力,下调炎性细胞因子IFN-γ和IL-1β水平,升高保护性细胞因子IL-10水平,促进CD4,CD25调节性T细胞比例增加。结论 Rho/Rock信号通路的激活在EAE的发病中起着重要作用,应用Rock抑制剂--Fasudil抑制EAE免疫病理过程中外周免疫细胞激活这一起始重要环节,减少炎性细胞的中枢浸润,缓解EAE的临床症状。
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| 关 键 词： | 多发性硬化 实验性自身免疫性脑脊髓炎 Rho激酶 盐酸法舒的尔 |
The Immunoloregulation of Fasudil,a Rho Kinase Inhibitor,in the Peripheral Immune System of Experimental Autoimmune Encephalomyelitis |
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| YU Jie-zhong,LI Yan-hua,LIU Chun-yun,YANG De-bing,MENG Jian,WANG Li-jun,XIAO Biao-guo,MA Cun-gen.The Immunoloregulation of Fasudil,a Rho Kinase Inhibitor,in the Peripheral Immune System of Experimental Autoimmune Encephalomyelitis[J].Journal of Yanbei Teachers College,2013(1):50-54,69. |
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| Authors: | YU Jie-zhong LI Yan-hua LIU Chun-yun YANG De-bing MENG Jian WANG Li-jun XIAO Biao-guo MA Cun-gen |
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| Institution: | 1.Institute of Brain Science,Shanxi Datong University,Datong Shanxi,037009; 2.Department of Neurology,the Affiliated Hospital of Shanxi Datong University,Datong Shanxi,037009; 3.Institutes of Brain Science and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai,200040) |
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| Abstract: | Objective To further explor the mechanism（s） of immunoloregulation underlying the amelioration in EAE caused by Fasudil,particularly focusing on anti-inflammatory effect in the peripheral immune system.Methods Female C57BL/6 mice immunized with MOG35-55 were randomly divided into CFA group,EAE group and Fasudil group.Fasudil was intraperitoneally injected in the dosage of 50 mg·kg·d on day 7 post-immunization（p.i.） for 14 consecutive days.Clinical signs were evaluated and body weight was recorded every other day.Mice were sacrificed on day 28 p.i.,and the pathological changes in spinal cords were detected by HE staining and demyelination staining.Spleen mononuclear cell（MNC） were isolated under asepsis.The proliferation assay and CD4 CD25 Treg proportion were determined,and the supernatants were harvested for the detection of IL-4、IL-10、IL-1β、IFN-γ.The expression of Rock in spleen and MNC was detected by immunofluorescence staining.Results： Fasudil hydrochloride may significant ameliorate symptoms of EAE,lessen inflammatory cell infiltration and demyelination,suppress the secretion of IFN-γ,IL-1β and promote the secretion of IL-10,the proportion of CD4 CD25 Treg.The expression of Rock in spleen and MNC was significantly upregulated in EAE.Conclusions： Fasudil,Rock inhibitor,ameliorates disease progression in EAE,acting possibly through anti-inflammatory and immunoloregulation pathway in the peripheral immune system. |
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| Keywords: | multiple sclerosis experimental autoimmune encephalomyelitis rock fasudil |
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