Prnp-SNCA-A53T帕金森病转基因小鼠肠道菌群差异  

Differences in gut microbiota of Prnp-SNCA-A53T Parkinson’s disease transgenic mice

作　　者：徐美玲 张帆 张瑜 桑明 王普清 XU Meiling;ZHANG Fan;ZHANG Yu;SANG Ming;WANG Puqing(Xiangyang No.1 People’s Hospital,Hubei University of Medicine,Xiangyang 441000,China;Hubei Clinical Research Center of Parkinson’s Disease,Xiangyang 441000)

机构地区：[1]湖北医药学院附属襄阳市第一人民医院,湖北襄阳441000 [2]湖北省帕金森病临床医学研究中心,湖北襄阳441000

出　　处：《中国实验动物学报》2021年第3期284-292,共9页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金项目(81703496);湖北医药学院校基金项目(FDFR201615);湖北医药学院药护学院团队项目(2017YHKT02);湖北医药学院研究生科技创新项目(YC2020027);湖北省实验动物资源开发及利用项目(2020DFE025);湖北省技术创新专项对外科技合作类(2019AHB068)。

摘　　要：目的多项证据表明帕金森病患者肠道菌群失调,而Prnp-SNCA-A53T帕金森病转基因小鼠是否也存在肠道菌群失调尚未见报道,本研究拟对该模型小鼠的肠道微生物生态特征进行分析。方法采用illumina高通量测序技术对7只雌性转基因小鼠及13只同性别同周龄野生型小鼠粪便微生物16S rRNA基因V3-V4区进行测序及生物信息分析,并用PICRUST预测差异功能通路。结果与野生型组相比,A53T组小鼠肠道微生物α多样性有增高趋势,而且微生物组成及物种也具有显著性差异:A53T组小鼠肠道微生物在门水平,放线菌门增高(P=0.0094),拟杆菌门降低(P=0.0498);在纲水平,红蝽菌纲增高(P<0.0001),拟杆菌纲降低(P=0.0398);在目水平,红蝽杆菌目增高(P<0.0001),拟杆菌目(P=0.0398)及红细菌目降低(P=0.0185);在科水平,红蝽杆菌科增高(P<0.0001),拟杆菌科(P=0.0277)及红杆菌科降低(P=0.0185);在属水平,伊格尔兹氏菌属增高(P=0.0002),拟杆菌属(P=0.0277)及红杆菌属降低(P=0.0249)。另外A53T组与野生型组在9个功能通路上存在显著差异,分别是G蛋白偶联受体、类固醇激素的合成、青霉素和头孢菌素的生物合成、泛醌和其他萜类醌的生物合成、甲苯降解的生物合成与代谢、聚糖的生物合成与代谢、电子转移载体、减数分裂以及非洲锥虫病。结论本研究结果表明转基因小鼠存在肠道菌群失调,同时转基因模型小鼠与野生型小鼠代谢通路存在差异,为后期研究肠道菌群菌与帕金森病的关联性提供了理论基础。Objective Evidence indicate that the gut microbiota of Parkinson’s disease patients is imbalanced,but whether the Prnp-SNCA-A53 T Parkinson’s disease transgenic mouse model also has gut microbiota imbalances is unknown.This study aimed to analyze the ecological characteristics of the gut microbiota of this mouse model.Methods Illumina high-throughput sequencing technology was performed to sequence and analyze the biological information of the 16 S rRNA gene V3–V4 region of the fecal microbiota in seven female transgenic mice and 13 wild-type mice of the same sex and age.PICRUST(Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)was used to predict the differential function pathways.Results Compared with the wild-type group,the gut microbial alpha diversity of mice in the A53 T group had a tendency to increase,and there were also significant differences in microbial composition and species.At the phylum level,the Actinobacteria were increased(P=0.0094),and the Bacteroidetes were decreased(P=0.0498).At the class level,the Coriobacteriia were increased(P<0.0001),and the Bacteroidia were decreased(P=0.0398).At the order level,the Coriobacteriales were increased(P<0.0001),while the Bacteroidales(P=0.0398)and the Rhodobacterales were decreased(P=0.0185).At the family level,the Coriobacteriaceae were increased(P<0.0001),while the Bacteroidaceae(P=0.0277)and the Rhodobacteraceae were decreased(P=0.0185).At the genus level,the Eggerthella were increased(P=0.0002),while the Bacteroides(P=0.0277)and the Rhodobacter were decreased(P=0.0249).In addition,there were significant differences between the A53 T group and the wild-type group in nine functional pathways,including G protein-coupled receptor,steroid hormone biosynthesis,penicillin and cephalosporin biosynthesis,ubiquinone and other terpenoid-quinone biosynthesis,toluene degradation,glycan biosynthesis and metabolism,electron transfer carriers,meiosis–yeast,and African trypanosomiasis.Conclusions This study indicated that there are

关 键 词：转基因模型小鼠 野生型小鼠 肠道菌群 菌群多样性 信号通路 

分 类 号：Q95-33[生物学—动物学]