摘要
目的:探讨黄芪甲苷(AST-Ⅳ)对实验性自身免疫性脑脊髓炎(EAE)小鼠的防治作用及作用机制。方法:C57BL/6雌性小鼠18只,采用髓鞘少突胶质细胞糖蛋白多肽35-55(MOG35-55)诱导建立EAE模型,随机分为EAE对照组,AST-Ⅳ高、低剂量组。造模的第3天起,进行注射用药,持续25d。EAE对照组腹腔注射PBS;AST-Ⅳ高、低剂量组分别腹腔注射AST-Ⅳ溶液30、15mg·kg^-1·d^-1;各组小鼠每次给药0.2mL/只,隔天记录体质量变化。HE染色检测脊髓炎细胞浸润。流式细胞术检测脾中CD_4^+T淋巴细胞表型的表达情况。Western Blot法检测脊髓TLR4、Myd88、NF-κB/p65的表达变化。结果:与EAE对照组比较,AST-Ⅳ高剂量组可显著降低平均最高临床评分(P<0.01),减轻EAE临床症状;抑制脊髓炎性细胞浸润;显著增加CD_(25)^+和TGF-β^+的CD_4^+T细胞亚群的比例(P<0.01),降低CD_4^+IL-17^+的比例(P<0.01),明显抑制TLR4、Myd88、NF-κB/p65在脊髓的表达(P<0.05,P<0.01)。结论:AST-Ⅳ可能通过调节Th17细胞与Treg细胞两者之间的平衡和调节炎性通路减轻EAE的发病程度。
Objective:To investigate the mechanism and efficacy of astragalosideⅣ(AST-Ⅳ)in the therapy of experimental autoimmune encephalomyelitis(EAE)mice.Methods:Eighteen C57BL/6 female mice were induced to establish EAE model by myelin-MOG35-55.All the mice were randomly divided into three groups,EAE control group,high doses of AST-Ⅳgroup,and low dose of AST-Ⅳgroup.After 3 days of modeling,the mice were injected with drug till 25 days.The EAE control group was injected with phosphate buffer saline(PBS)through abdominal cavity;the AST-Ⅳhigh-dose group and the AST-Ⅳlow-dose group were injected with AST-Ⅳ30 mg·kg^-1·d^-1 and 15 mg·kg^-1·d^-1 into the abdominal cavity,respectively;every mice in each group were given 0.2 mL/d.The weight changes were recorded every other day.Since 9th day recorded the clinical scores and symptoms of the mice.At the end,HE staining was used to find infiltration of spinal cord;the expression of CD4+T lymphocyte phenotype in spleen was detected by flow cytometry;Western blot was used to detect the expression of TLR4 signaling pathway,MYD88 and NF-κB/p65 in spinal cord.Results:Compared with EAE control group,AST-Ⅳhigh-dose could significantly reduce the average highest clinical score(P<0.01),and alleviate the clinical symptoms of EAE.AST-Ⅳcould inhibit the inflammatory cells in spinal cord,significantly increased the proportion of CD4+T cells subsets of CD25+and TGF-β+,decrease the proportion of CD4+IL-17+(P<0.01).Inhibiting the expression of TLR4,Myd88 and NF-κB/p65 in spinal cord(P<0.05,P<0.01).Conclusion:AST-Ⅳcan reduce the incidence of EAE by regulating the inflammatory pathway and can adjust the balance between Th17 cells and Treg T cells.
作者
刘建春
张红珍
郭文娟
柴智
尉杰忠
于婧文
肖保国
马存根
LIU Jian-chun;ZHANG Hong-zhen;GUO Wen-juan;CHAI Zhi;WEI Jie-zhong;YU Jing-wen;XIAO Bao-guo;MA Cun-gen(Research Center of Neurobiology,Shanxi University of Traditional Chinese Medicine,The Key Research Laboratory of Benefiting Qi for Activating Blood Circulation to Treat Multiple Sclerosis,National Administration of Traditional Chinese Medicine,Jinzhong 030619,China;institute of Brain Science,Shanxi Datong University,Datong 037009,China;Institute of Neurology,Huashan Hospital,Fudan University,Shanghai 200025,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2020年第6期3119-3122,共4页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金面上项目(No.81473577)
黄芪资源产业化及产业国际化协同创新中心项目(No.HQXTCXZX2016-020)
山西中医药大学科技创新能力培育计划项目(No.2019PY-027)。
