敲除ST2表达对ConA诱导的自身免疫性肝炎小鼠肠道菌群的影响  

Effect of knockout ST2 expression on intestinal microflora in mice with ConAinduced autoimmune hepatitis

作　　者：江仁权 汤纪丰 何毓珏[1] 夏锦芳 林锦骠[1] 欧启水[1] JIANG Renquan;TANG Jifeng;HE Yujue;XIA Jinfang;LIN Jinpiao;OU Qishui(Department of Laboratory Medicine,National Reginal Medical Center of Binhai Campus,Fujian Key Laboratory of Laboratory Medicine,Gene Diagnosis Research Center,Fujian Clinical Research Center for Clinical Immunology Laboratory Test,the First Affiliated Hospital,Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院检验科,福建医科大学附属第一医院滨海院区国家区域医疗中心检验科,福建省检验医学重点实验室,福建医科大学基因诊断研究中心,福建省临床免疫学检验临床医学研究中心,福州350005

出　　处：《中国免疫学杂志》2025年第3期529-534,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(82072356);福建省卫生健康青年科研课题(2021QNA030)。

摘　　要：目的:通过敲除生长刺激表达基因2(ST2)表达探讨其对ConA诱导的自身免疫性肝炎(AIH)小鼠肠道菌群的影响。方法:借助基因敲除技术,构建ST2基因敲除小鼠,在此基础上采用ConA诱导建立AIH小鼠模型;通过实时荧光定量PCR(RT-PCR)检测细胞因子相对表达量;使用16S rRNA高通量测序方法进行肠道微生物测序,测序结果采用Microbial Ecology相关软件和数据库进行分析。结果:与对照组相比,在敲除ST2基因后,ConA诱导的AIH小鼠血清中ALT和AST水平降低,肝脏损伤较轻且IL-6相对表达量也降低;反应菌群分布丰度的ACE和CHAO指数无明显差异;反映菌群多样性的Shannon和Simpson指数无明显差异;Psychrobacter、unclassified_Clostridia、Halothiobacillus、Clostridium_XlVa和Haemophilus菌属含量增加;Romboutsia、Rikenella、Parabacteroides和unclassified_Clostridiales菌属含量减低,其受试者工作特征(ROC)曲线下面积分别为0.88、0.89、0.88、0.80、0.90、0.90、0.84、0.91和0.84。结论:在AIH小鼠体内敲除ST2基因表达可减轻肝损伤及炎症,不影响肠道菌群的分布丰度及多样性,但菌属间具有差异性,且具有良好的诊断价值。Objective:To investigate the effect of growth stimulation expressed gene 2(ST2)on intestinal microflora of mice with ConA-induced autoimmune hepatitis(AIH)by knockout.Methods:ST2 gene knockout mice were constructed by gene knockout technique.On this basis,AIH mouse model was established by ConA induction.The relative expression of cytokines was detected by real-time fluorescence quantitative PCR(RT-PCR).Intestinal microorganisms were sequenced using the 16S rRNA high-through put sequencing method,and the sequencing results were analyzed using Microbial Ecology related software and database.Results:Compared with the control group,ALT and AST were decreased,the damage of liver was mild,and the relative expression of IL-6 was also decreased in the liver of mice with ConA-induced AIH after ST2 gene knockout.There was no significant difference in the ACE and CHAO indices of the abundance of reactive flora.There was no significant difference between Shannon index and Simpson index reflecting bacterial diversity.Psychrobacter,unclassified_Clostridia,Halothiobacillus,Clostridium_XlVa and Haemophilus genus content increased;Romboutsia,Rikenella,Parabacteroides and unclassified_Clostridiales bacterial content reduce.The areas under the receiver operator characteristic(ROC)curves were 0.88,0.89,0.88,0.80,0.90,0.90,0.84,0.91 and 0.84,respectively.Conclusion:Knockout of ST2 gene expression in mice with AIH can reduce liver injury and inflammation,and does not affect the distribution abundance and diversity of intestinal flora.However,there are differences among bacteria genera,and it has good diagnostic value.

关 键 词：ST2敲除小鼠 刀豆蛋白A 肠道菌群 自身免疫性肝炎 诊断价值 

分 类 号：R593.22[医药卫生—内科学]