表达谱测序分析不同病程糖尿病大鼠心肌差异表达基因  

RNA-seq Analysis of Differential Expressed Genes in the Myocardium of Type 2 Diabetic Rats

作　　者：谭茵[1,2] 雷艳萍 黄程 李晓媚[1] 熊燕[1,3] Tan Yin;Lei Yanping;Huang Cheng;Li Xiaomei;Xiong Yan(Guangzhou Institute of Snake Venom Research,Guangzhou Medical University,Guangzhou,511436;GMU and GIBH School of Life Sciences,Guangzhou Medical University,Guangzhou,511436;The Central Laboratory,The Fifith Affiliated Hospital of Guangzhou Medical University,Guangzhou,510700)

机构地区：[1]广州医科大学,广州蛇毒研究所,广州511436 [2]广州医科大学,广医-广州生物院联合生科院,广州511436 [3]广州医科大学附属五院实验中心,广州510700

出　　处：《基因组学与应用生物学》2020年第12期5419-5431,共13页Genomics and Applied Biology

基　　金：国家自然科学基金(81570751);广东省自然科学基金重点项目(2016A030311050)共同资助。

摘　　要：本研究采用表达谱测序方法分析不同病程2型糖尿病(T2DM)大鼠心肌差异表达基因。采用高脂饲养加小剂量链脲佐菌素(STZ,30 mg/kg,i.p.)方法诱导8~16 w的T2DM大鼠模型,用M-型超声心动仪检测大鼠心脏结构及功能并对心肌组织进行表达谱测序。利用生物信息学方法对各组所得的显著差异表达基因(DEGs)进行表达水平检测分析,在各数据库进行基因注释比对;获得DEGs功能注释、GO功能分析及KEGG富集通路分析。大鼠口服糖耐量试验结果显示,与正常对照比较,8~16 w T2DM大鼠空腹血糖明显升高而糖耐量降低,提示T2DM模型制备成功;M-超声心动图结果显示,8 w-T2DM大鼠左心室舒张和收缩功能障碍,16 w-T2DM大鼠还伴有心脏形态和结构的损害,提示糖尿病心肌病(DCM)形成。各组有18410个基因和19184 Unigenes获得GO注释;8~16 w T2DM大鼠所获360和381个DEGs分别富集于19个细胞组分、21个分子功能条目和22个生物过程条目;KEGG通路分析表明,DEGs主要富集于脂肪代谢信号通路等方面。通过对不同病程的T2DM大鼠心肌进行表达谱测序分析揭示了在DCM发生发展过程中所呈现的DEGs,为深入研究DCM发病分子机制及临床防治和药物研发提供潜在靶点。This study is to investigate the differential expressed genes(DEGs)in the myocardium of type 2 diabetic(T2DM)rat based on transcriptome sequencing techniques.T2DM rat model was induced by intraperitoneal injection of a low dose streptozotocin(STZ,30 mg/kg,i.p)as a bolus plus high-fat diet for 8~16 weeks,respectively.Rats were anesthetized by intraperitoneal injection of chloral hydrate(300 mg/kg,i.p),and cardiac function was detected by M-mode echocardiography.The myocardial tissue was sent to transcriptome sequencing.The bioinformative means were used to analyze the expression level of differential expressed genes(DEGs)obtained from experimental groups and acquire the gene annotation based on the multiple databases description,DEGs’function annotation,GO analysis and the KEGG enriched pathway analysis.Oral glucose tolerance test(OGTT)showed that the fasting blood glucose level was significantly elevated,and glucose tolerance was impaired in 8~16 w T2DM rats compared with their control groups,indicating that T2DM rat model was well build.The M-mode echocardiogram presented that both diastolic and contract functions of left ventricle were distinctly impaired in the hearts of8~16 w T2DM rats in comparison with their control groups.Furthermore,16 w T2DM rats were exhibited apparent abnormal in their cardiac morphology and structure,which confirmed that the DCM rat model was successfully established.There are 18410 genes and 19184 Unigenes obtained GO annotated in each group.Totally 360 and 381 DEGs from 8~16 w T2DM have been enriched in 19 cellular components,21 molecular functions,and 22 biological processes.KEGG pathway analysis showed that the DEGs enriched in several pathways including fatty acid metabolism.The present study reveals the DEGs in the myocardium of T2DM rats with different course of the disease during the development of DCM by the transcriptome sequencing.It also helps to further investigate the molecular mechanism of DCM and screen the potential target for treatment of DCM and new drug developme

关 键 词：2型糖尿病 糖尿病心肌病 表达谱测序 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]