基于肠道菌群探讨电针对APP/PS1小鼠认知能力的改善机制  

Electroacupuncture improves cognitive ability of APP/PS1 mice based on mechanism of affecting gut microbiota

作　　者：廖冬梅 庞芳 杨云昊 夏青倩 李怡 郭啸 唐成林[1] LIAO Dong-mei;PANG Fang;YANG Yun-hao;XIA Qing-qian;LI Yi;GUO Xiao;TANG Cheng-lin(College of Traditional Chinese Medicine,Chongqing Medical University,Chongqing 400016,China;College of Basic Medicine,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学中医药学院,重庆400016 [2]重庆医科大学基础医学院,重庆400016

出　　处：《中国病理生理杂志》2021年第10期1774-1783,共10页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金项目(No.81273870);重庆市科卫联合中医药科技项目(No.ZY201801007);重庆市渝中区科技计划项目(No.20200116)。

摘　　要：目的:观察电针对APP/PS1双转基因小鼠肠道菌群及相关炎症因子表达的影响,探讨其对小鼠认知能力的改善机制。方法:14只5月龄APP/PS1雄性小鼠随机分成模型组和电针组,同月龄C57BL/6雄性小鼠作为对照组,每组7只。电针组选取"百会"、"大肠俞"和"足三里"穴干预,连续波,频率2 Hz,强度1.0 mA,每日1次,每次15 min,1周5次,连续5周。Morris水迷宫评估小鼠认知能力;Western blot检测结肠组织核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)的表达;ELISA检测结肠组织及血清中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)和IL-18的含量;16S rDNA扩增子测序法检测小鼠粪便菌群。结果:与对照组相比,从训练第2天开始,模型组小鼠逃避潜伏期延长(P<0.05),第3天开始,其穿越平台次数显著减少(P<0.05);此外,相较对照组,模型组结肠组织中NLRP3表达显著增加,结肠组织及血清中TNF-α,IL-1β和IL-18含量均显著增高(P<0.01)。与模型组相比,电针组逃避潜伏期下降趋势显著,第5天其逃避潜伏期缩短、穿越平台次数增加(P<0.05),结肠组织中NLRP3表达,TNF-α、IL-1β和IL-18含量均降低(P<0.05),血清TNF-α、IL-1β和IL-18含量降低(P<0.05)。肠道菌群结果显示,在门水平,相较于对照组,模型组拟杆菌门相对丰度增高(P<0.05),厚壁菌门、Patescibacteria、软壁菌门等相对丰度降低(P<0.05);在属水平,模型组乳杆菌、副拟杆菌等相对丰度降低(P<0.05),副萨特氏菌、理研菌等相对丰度增高(P<0.05)。在门水平,电针组拟杆菌门相对丰度较模型组降低,厚壁菌门、Patescibacteria、软壁菌门等相对丰度较模型组轻度增高,差异均无统计学意义(P>0.05);属水平上,相较于模型组,电针组副萨特氏菌、理研菌等相对丰度降低(P<0.05),Candidatus Saccharimonas、Muribaculum等相对丰度增高(P<0.05),而乳杆菌、副拟杆菌、双歧杆菌等相对丰度增高,但差异无统计学意义(P>0.05)。结论:电针AIM:To observe the effects of electroacupuncture(EA)on gut microbiota and the expression of related inflammatory factors in APP/PS1 double transgenic mice,so as to explore the mechanism underlying improvement of cognitive ability in APP/PS1 mice.METHODS:Male APP/PS1 mice(5-month-old)were randomly divided into model group and EA group,male C57 BL/6 mice of the same age was used as control group(7 in each group). EA(2 Hz,1. 0 mA)was applied to"Baihui"(GV 20),"Dachangshu"(BL 25)and"Zusanli"(ST 36)for 15 min,once daily,5 days per week for 5 weeks. The Morris water maze was used to detect the cognitive ability of the mice. The expression of nucleotide binding oligomerization domain-like receptor protein 3(NLRP3)in colon tissue was determined by Western blot. The contents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-18 in colon tissue and serum were measured by ELISA. 16 S rDNA amplicon sequencing was used to observe the microflora in the feces of the mice.RESULTS:Compared with control group,the escape latency in model group was prolonged from the second day of training(P<0. 05),and the number of crossing the platform was significantly decreased from the third day of training(P<0. 01). In addition,the expression of NLRP3 in colon tissue was significantly increased(P<0. 01),the contents of TNF-α,IL-1β and IL-18 in colon tissue and serum were significantly increased in model group compared with control group(P<0. 01). Compared with model group,the escape latency in the EA group was significantly decreased,the escape latency shortened,and the number of crossing the platform increased on the 5 th day of training(P<0. 05). The expression of NLRP3 and contents of TNF-α,IL-1β and IL-18 in colon tissue were decreased,and the contents of TNF-α,IL-1β and IL-18 in serum were decreased in EA group compared with model group(P<0. 05). Compared with control group,the relative abundance of Bacteroidetes in model group was increased(P<0. 05),while the relative abundances of Firmicutes,Patescibacteria and Tene

关 键 词：阿尔茨海默病 肠道菌群 电针 炎症 认知 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R363.2[医药卫生—临床医学]