首页|基于转录组测序技术探索1型糖尿病肝损伤的作用机制

基于转录组测序技术探索1型糖尿病肝损伤的作用机制

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目的:利用转录组测序的方法分析链脲佐菌素(STZ)诱导的1型糖尿病肝损伤大鼠模型组和对照组大鼠肝组织mRNA的表达情况,确定关键基因,讨论过氧化物酶体增殖物激活受体(PPARs)信号通路在该模型中的作用.方法:将20只SD雄性大鼠随机分为模型组和对照组,模型组一次性腹腔注射60 mg/kg STZ,对照组注射等量溶解液,第3天鉴定模型是否构建成功.通过RNA-seq寻找大鼠肝脏组织中差异表达基因,进行差异表达基因的功能富集,绘制蛋白质互作网络图,利用MCC、MNC、DMNC三种算法分别获得关键基因.结果:和对照组相比,模型组大鼠空腹血糖明显升高,肝脏病理染色(HE染色和油红O染色)显示有轻度脂肪变性.随后我们对肝脏组织的差异表达基因按照|log2FC|>1和P<0.05的标准进行筛选,和对照组相比模型组中有298个基因高表达,212个基因低表达.利用KEGG、GO以及GOKEGG联合log2FC进行富集分析时,其中富集到细胞组分、生物过程和分子功能的通路分别有282条、26条、9条,KEGG富集分析发现了 19条信号通路.通过MCC、MNC、DMNC三种算法得到的3个基因集合两两取交集可得到8个关键基因:Top2a、Kif11、Plk1、Ttk、Bub1、Cdk1、Ccna2、Cdc20.结论:通过RNA-seq筛选了STZ诱导的1型糖尿病肝损伤大鼠模型中的差异表达基因,发现PPARs信号可能在其中发挥了一定的作用,其具体机制有待进一步阐明.
Exploring the mechanism of liver injury in type 1 diabetes based on transcriptome sequencing technology
Objective:To analyze the mRNA expression in the liver tissue of streptozotocin(STZ)-induced liver injury in type 1 diabetic rats and control rats,identify the hub genes and discuss the role of peroxi-some proliferator-activated receptors(PPARs)signaling pathway in this model.Methods:A total of twenty SD male rats were randomly divided into the model group and control group.The model group received a single intraperitoneal injection of 60 mg/kg of STZ while the control group received the same amount of dissolved solution.The fasting blood glucose levels and liver pathology were mea-sured to assess the success of the modeling on the third day.Then we searched for differentially ex-pressed genes in rat liver tissues by RNA-seq,performed functional enrichment of differentially ex-pressed genes,and mapped protein interaction networks.Hub genes were acquired by MCC,MNC,and DMNC algorithms.Results:Compared to the control group,fasting blood glucose was signifi-cantly higher in the model rats,and pathological staining of the liver(HE stain and Oil Red O stain)showed mild steatosis.We then screened the liver tissue for differential genes based on |log2FC|>1 and P<0.05.We identified 298 genes that were highly expressed and 212 genes that were lowly ex-pressed in the model group as compared with those in the control group.Enrichment analysis by KEGG,GO and GOKEGG,and log2FC(P.adj<0.1)revealed that in addition to the 19 signaling pathways identified by KEGG analysis,we found 282 signaling pathways enriched in cellular compo-nents,26 signaling pathways enriched in bioprocesses,and 9 pathways enriched in molecular func-tions.Eight hub genes Top2a,Kif11,Plk1,Ttk,Bub1,Cdk1,Ccna2,and Cdc20 can be acquired by taking the intersection of the three gene sets obtained by the three algorithms of MCC,MNC and,DMNC.Conclusion:The differentially expressed genes in the STZ-induced liver injury in type 1 dia-betic rats were screened by RNA-seq,and it was found that PPARs signaling may play a role in this disease,and the precise mechanism needs to be further clarified.

Type 1 DiabetesStreptozotocinLiver InjuryPeroxisome Proliferator-Activated Receptors(PPARs)RNA-seq

张腊英、金柳荫、何安玲、肖勇、陈明锴

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武汉大学人民医院消化内科 湖北 武汉 430060

武汉大学人民医院精神卫生中心 湖北 武汉 430060

1型糖尿病 链脲佐菌素 肝损伤 过氧化物酶体增殖物激活受体 RNA-seq

湖北省重点研发计划

2020BCB007

2024

武汉大学学报(医学版)
武汉大学

武汉大学学报(医学版)

CSTPCD
影响因子:0.959
ISSN:1671-8852
年,卷(期):2024.45(5)
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