不同性别大鼠NMBA致食管癌前病变成模及肠道菌群和代谢组学分析  

Modeling of precancerous esophageal lesions induced by NMBA in rats of different genders and analysis of intestinal microbiota and metabolomics

作　　者：张晨辰 刘亚平 高晓璐 王志超[2] 李胜超[2] 史会娟[2] ZHANG Chen-chen;LIU Ya-ping;GAO Xiao-lu;WANG Zhi-chao;LI Sheng-chao;SHI Hui-juan(Graduate School of Hebei Medical University,Shijiazhuang 050017,China;Department of Traditional Chinese Medicine,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China)

机构地区：[1]河北医科大学研究生学院,河北石家庄050017 [2]河北医科大学第四医院中医科,河北石家庄050011

出　　处：《河北医科大学学报》2025年第3期291-297,共7页Journal of Hebei Medical University

基　　金：河北省自然科学基金(H2021206010)。

摘　　要：目的探讨雌鼠与雄鼠制备食管癌前病变模型中肠道菌群及代谢组学的差异。方法给予雌鼠模型组大鼠及雄鼠模型组大鼠皮下注射N-亚硝基甲基氨基丁酸(N-Nitorsos-N-methyl-4-aminobutyric Acid,NMBA)溶液(0.30 mg/kg,3 d/次);对照组大鼠不予诱导;应用HE染色观察各组大鼠食管黏膜病理组织学情况;从大鼠盲肠内容物中提取总DNA,应用16S rRNA基因测序和生物信息学分析进行肠道菌群α和β多样性分析,获取组间的差异菌;应用非靶向代谢组学检测血浆代谢产物。结果大鼠食管上皮HE染色结果显示,大鼠经NMBA处理40周后,雄鼠造模较雌鼠更为稳定;16S rRNA基因测序结果显示,2组样品中物种丰度以及均匀度差异无统计学意义,而各个群落的数量和分布的差异性较大,在属水平,雌鼠模型组与雄鼠模型组的肠道菌群表达有明显不同;代谢组学结果显示雄鼠模型组与雌鼠模型组大鼠血液代谢明显不同,其差异明显的代谢物主要集中在氧化脂质及胆汁酸。结论雌鼠与雄鼠制备食管癌前病变模型中肠道菌群及代谢组学存在明显不同。Objective To explore the difference of intestinal microbiota and metabonomics between male and female rats in the preparation of precancerous esophageal lesion models.Methods N-Nitorsos-N-methyl-4-aminobutyric Acid(NMBA)solution(0.30 mg/kg)was subcutaneously injected into female rats and male rats every 3 days.The rats in the control group were not induced,and HE staining was used to observe the pathological histology of esophageal mucosa in each group.Total DNA was extracted from the contents in the cecum of rats,and 16S rRNA gene sequencing and bioinformatics analysis were used to analyze theαandβdiversity and then obtain the different bacteria between groups.Non-targeted metabonomics was used to detect metabolites of plasma.Results The HE staining results of rat esophageal epithelium showed that after 40 weeks of treatment with NMBA,male rats showed more stable modeling compared with female rats.The 16S rRNA gene sequencing results showed that there was no significant difference in species abundance and evenness of the samples between the two groups,while there were significant differences in the number and distribution of each community.At the genus level,there were significant differences in the expression of intestinal microbiota between the female and male mouse model groups.The metabolomics results showed that there were significant differences in blood metabolism between the male and female mouse model groups,and the metabolites with significant differences were mainly concentrated in oxidized lipids and bile acids.Conclusion There are significant differences in intestinal microbiota and metabolomics between female and male mice in the preparation of esophageal precancerous lesion models.

关 键 词：食管肿瘤 大鼠 成瘤率 肠道菌群 代谢组学 

分 类 号：R735.1[医药卫生—肿瘤]