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高脂饮食影响小鼠肠道免疫功能的转录组分析

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目的 研究高脂饲喂对小鼠肠道免疫功能及相关基因表达的影响,并探讨高脂饮食导致肠道炎症和影响肠道屏障功能的潜在机制。方法 2019年6月,将24只C57BL/6J雄性小鼠分为正常饮食组(CON组)和高脂饮食组(HFD组),每组12只,采用随机分组法分为4笼,每笼3只,分别饲喂18周。采用酶联免疫吸附试验试剂盒检测血糖、血脂等生化指标。采用Trizol试剂法提取小鼠盲肠组织总RNA,逆转录获得cDNA并建库进行RNA转录组测序,利用基因本体、京都基因与基因组百科全书数据库对差异表达基因进行功能分析和通路富集分析。结果 HFD组小鼠第18周体重[(36。96±1。31)g],以及空腹血糖(GLU)[(6。65±0。41)mmol/L]、低密度脂蛋白胆固醇[(0。97±0。07)mmol/L]、总胆固醇[(4。08±0。15)mmol/L]、甘油三酯[(0。64±0。03)mmol/L]水平均明显高于 CON 组[分别为(31。81±0。53)g,(4。53±0。33)、(0。60±0。04)、(2。79±0。13)、(0。51±0。02)mmol/L],差异均有统计学意义(t=3。66、4。00、4。46、6。34、3。52,P=0。001 4、0。000 6、0。000 2、<0。000 1、0。002 0)。盲肠组织差异表达基因主要富集到免疫和细胞死亡等多个生物学过程,其中cxcr4、ccr7、cxcl12、ccl28、cxcl13、ccl21a等主要炎症因子明显上调,高脂饮食明显降低了肠道屏障功能重要基因cndl4的表达,可能导致屏障功能受损。结论 高脂饮食可明显影响肠道免疫功能,并可能诱导肠道屏障功能受损,是肠道炎症及炎性相关疾病的潜在致病因素。
Transcriptome analysis of high-fat diet affecting intestinal immune function in mice
Objective To investigate the effects of high-fat feeding on intestinal immune function and related gene expression in mice,and to explore the potential mechanisms by which a high-fat diet leads to in-testinal inflammation and affects intestinal barrier function.Methods In June 2019,A total of 24 C57BL/6J male mice were divided into a normal diet group(CON group)and a high-fat diet group(HFD group),with 12 mice in each group,using the random grouping methed,divided into 4 cages with 3 mice in each cage,and fed for 18 weeks respectively.Enzyme-linked immunosorbent assay(ELISA)kits were used to detect bio-chemical indexes such as blood glucose and blood lipids.Total RNA of mouse cecum tissue was extracted by Trizol reagent method,cDNA was obtained by reverse transcription and libraries were constructed for RNA transcriptome sequencing,and differentially expressed genes were subjected to functional analysis and pathway enrichment analysis by using Gene Ontology,Kyoto Genome and Genome Encyclopedia databases.Results The body weight[(36.96±1.31)g],and GLU[(6.65±0.41)mmol/L],LDL cholesterol[(0.97±0.07)mmol/L],total cholesterol[(4.08±0.15)mmol/L],and triacylglycerol[(0.64±0.03)mmol/L]of the mice in the HFD group at week 18 levels were significantly higher than those in the CON group[(31.81±0.53)g,(4.53±0.33),(0.60±0.04),(2.79±0.13),and(0.51±0.02)mmol/L,respectively],and the differences were statistically significant(t=3.66,4.00,4.46,6.34,3.52,P=0.001 4,0.000 6,0.000 2,<0.000 1,0.002 0).The differentially expressed genes in cecum tissues were mainly enriched to several biologi-cal processes such as immunity and cell death,in which the major inflammatory factors such as cxcr4,ccr7,cx-cl12,ccl28,cxc113,and ccl21a were significantly up-regulated,and the high-fat diet markedly reduced the im-portant genes for the intestinal barrier function,the cndl4 expression,which may lead to impaired barrier func-tion.Conclusion A high-fat diet can significantly affect intestinal immune function and may induce impaired intestinal barrier function,which is a potential causative factor for intestinal inflammation and inflammation-related diseases.

High-fat dietMiceIntestineImmunityTranscriptome

周文汀、周一征、王舜、邱熠、何如怡、田宇、刘志国

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武汉轻工大学生命科学与技术学院,湖北武汉 430023

高脂饮食 小鼠 肠道 免疫功能 转录组

2024

现代医药卫生
重庆市卫生信息中心

现代医药卫生

影响因子:0.758
ISSN:1009-5519
年,卷(期):2024.40(23)