粪菌移植对实验性自身免疫性脑脊髓炎小鼠肠道功能及细胞因子的影响  

Effect of fecal microbiota transplantation on intestinal function and cytokines in experimental autoimmune encephalomyelitis mice

作　　者：王志豪 李作孝 WANG Zhihao;LI Zuoxiao(Department of Neurology,The Affiliated Hospital of Southwest Medical University,Luzhou Sichuan 646000,China)

机构地区：[1]西南医科大学附属医院神经内科,646000

出　　处：《中国神经免疫学和神经病学杂志》2020年第3期169-173,共5页Chinese Journal of Neuroimmunology and Neurology

基　　金：泸州市人民政府-西南医科大学科技战略合作资金项目(2018LZXNYD-ZK17)。

摘　　要：目的探讨粪菌移植(fecal microbiota transplantation,FMT)对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)小鼠发病、肠道功能和细胞因子白细胞介素-1β(IL-1β)、IL-6、肿瘤坏死因子-α(TNF-α)的影响。方法选择30只清洁级SPF级雌性C57BL/6小鼠,随机分为正常对照组、EAE模型组、FMT干预组,每组10只。采用髓鞘少突胶质细胞糖蛋白肽35-55(MOG35-55)抗原免疫法制备EAE模型。FMT干预组于造模第2天给予粪便滤液0.4 mL灌胃,1次/d,共14 d;正常对照组、EAE模型组以相同方式给予等量生理盐水灌胃。观察各组小鼠发病情况;于EAE模型组和FMT干预组发病高峰时、正常对照组28 d时取小鼠粪便定量检测肠道菌群数量,计算双歧杆菌与肠杆菌的比值(Bifidobacterium/Enterobacter value,B/E值);ELISA法检测各组小鼠血清、脑组织IL-1β、IL-6、TNF-α的表达。结果与EAE模型组比较,FMT干预组小鼠发病潜伏期、达高峰期时间延迟,神经功能评分减低(均P<0.05)。EAE模型组B/E值小于1,FMT干预组B/E值大于1,且FMT干预组B/E值较EAE模型组高(P<0.05)。与正常对照组比较,EAE模型组血清和脑组织IL-1β、IL-6、TNF-α表达水平均增加(均P<0.05),而FMT干预组IL-1β、IL-6、TNF-α表达水平较EAE模型组减低(均P<0.05)。结论EAE小鼠存在肠道菌群紊乱,定植抗力差,细胞因子表达升高;FMT能改善EAE小鼠肠道菌群紊乱,提高肠道定植抗力,减轻炎症反应和神经功能障碍。Objective To investigate the effects of fecal microbiota transplantation(FMT)on the pathogenesis,intestinal function,and cytokines[interleukin-1(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α)]of experimental autoimmune encephalomyelitis(EAE)mice.Methods Thirty clean-grade SPF female C57BL/6 mice were selected and randomly divided into a normal control group,an EAE model group and an FMT intervention group,with 10 rats in each group.The EAE model was established using myelin oligodendrocyte glycoprotein peptide(MOG35-55)by antigen immunoassay.The FMT intervention group was intragastrically administered with 0.4 mL of fecal filtrate since the next day of modeling,once a day for a total of 14 days.The normal control group and the EAE model group were given the same amount of saline on the same way.We observed the disease progression in each group,and quantitatively detected the intestinal flora of mouse feces at the peak of disease in the EAE model group and the FMT intervention group,and in the normal control group after 28 days.We calculated the ratio of Bifidobacterium to Enterobacter bacteria(Bifidobacterium/Enterobacter value,B/E value)and detected IL-1β,IL-6,and TNF-αlevels in serum and brain tissue by ELISA.Results Compared with the EAE model group,the onset latency and peak period of mice in the FMT intervention group were delayed,and the neurological score was reduced(P<0.05).The B/E value of the EAE model group was less than 1,the B/E value of the FMT intervention group was greater than 1,and the B/E value of the FMT intervention group was higher than that of the EAE model group(P<0.05).Compared with the normal control group,the expression levels of IL-1β,IL-6 and TNF-αin serum and brain tissue of the EAE model group were increased(P<0.05),while the expression levels of IL-1β,IL-6 and TNF-αin the FMT intervention group were lower than those in the EAE model group(P<0.05).Conclusions EAE mice have intestinal flora disorders,poor colonization resistance,and increased cytokine expression.FMT can impr

关 键 词：肠道菌群 粪菌移植 脑脊髓炎 自身免疫性 实验性 多发性硬化 肠道功能 白细胞介素1Β 白细胞介素6 肿瘤坏死因子α 

分 类 号：R744.51[医药卫生—神经病学与精神病学]