Git2基因敲除改变肠道菌群缓解小鼠NEC肠道损伤  

Git2 gene knockout alleviates intestinal injury of NEC in mice by altering intestinal flora

作　　者：王燕燕 龚自珍[1,2,3] 田春艳 王建 吴瑾 WANG Yan-yan;GONG Zi-zhen;TIAN Chun-yan;WANG Jian;WU Jin(Xinhua Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai 200092,China;Shanghai Institute forPediatric Research,Shanghai 200092,China;Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition,Shanghai 200092,China;Institute of Lifeomics,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 102206,China)

机构地区：[1]上海交通大学医学院附属新华医院,上海200092 [2]上海市儿科医学研究所,上海200092 [3]上海市小儿消化与营养重点实验室,上海200092 [4]军事科学院军事医学研究院生命组学研究所,北京102206

出　　处：《军事医学》2022年第6期435-440,共6页Military Medical Sciences

基　　金：上海市自然科学基金(20ZR1446200)。

摘　　要：目的研究G蛋白偶联受体激酶相互作用蛋白2(GIT2)基因敲除所致的小鼠肠道菌群改变及其在坏死性小肠结肠炎(NEC)发病中的作用。方法对Git2基因敲除(KO)小鼠和野生型(WT)小鼠肠道微生物基因组进行16S rRNA测序,分析其微生物多样性和菌群分类学组成,利用京都基因与基因组数据库(KEGG)功能通路预测比较两组小鼠肠道微生物功能差异;在WT小鼠、KO小鼠以及经抗生素处理的上述小鼠中诱导NEC疾病模型,观察各组小鼠肠道组织病理学改变情况。结果Git2基因敲除引起小鼠肠道微生物群落组成改变,与WT小鼠相比,KO小鼠肠道菌群中厚壁菌门和乳杆菌属占比增多,而大肠杆菌志贺菌属占比显著降低;在两种小鼠中诱导NEC,KO小鼠肠道病理损伤较WT小鼠明显减轻,而抗生素清除肠道菌群后KO小鼠肠道损伤情况与WT小鼠相比无明显差异。结论Git2基因敲除可能通过调节肠道菌群对NEC的肠道损伤发挥保护作用。Objective To investigate the alteration of intestinal flora in G-protein-coupled receptor kinase interacting proteins 2(GIT2)gene knockout mice and the contributions of knockout to the pathogenesis of necrotizing enterocolitis(NEC).Methods 16 S rRNA sequencing was performed on the gut microbial genomes of Git2 gene knockout(KO)mice and wild type(WT)mice to analyze their microbial diversity and taxonomic composition.The functional differences in intestinal flora between the two groups were predicted via Kyoto Encyclopedia of Genes and Genomes(KEGG)functional pathway analysis.In addition,NEC was induced in WT mice,KO mice and antibiotics-treated mice,and histopathological injuries to the intestines were analyzed.Results Git2 konckout changed the composition of the gut microbial community in mice.Compared to WT mice,the percentage of Firmicutes and Lactobacillus in the intestinal flora of KO mice was obviously increased,while that of Escherichia-Shigella was significantly reduced.Histopathological injuries to the intestine of KO NEC mice were much less severe than those in WT mice.No significant differences in intestinal damage were observed between KO NEC and WT NEC mice upon antibiotics treatment.Conclusion Git2 gene knockout may protect against intestinal injuries in NEC by regulating intestinal flora.

关 键 词：G蛋白偶联受体激酶相互作用蛋白2 基因敲除 肠道菌群 新生儿 坏死性小肠结肠炎 

分 类 号：R722.1[医药卫生—儿科]