摘要
目的:比较β-氨基丙腈(β-aminoacetonitrile,BAPN)和BAPN联合血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)诱导的两种小鼠主动脉夹层(aortic dissection,AD)模型的转录组学特征.方法:3周龄,雄性,30只C57BL/6J小鼠,随机分为两组:对照组(Ctrl-1)10只,BAPN诱导的AD模型组(BAPN)20只,模型组饲喂含0.4％BAPN的鼠粮3周.8～10周龄小鼠30只随机分为两组:对照组(Ctrl-2)10只,BAPN联合Ang Ⅱ诱导的AD模型组(BAPN+Ang Ⅱ)20只,模型组给予Ang Ⅱ(1 000 ng·kg-1·min-1)持续灌注4周,前2周饲喂含0.15％BAPN的鼠粮.两种模型分别采集主动脉大体图像分析AD形成部位,主动脉切片进行弹力纤维(elastic Verhoeff's Van Gieson,EVG)染色评估弹力纤维紊乱.主动脉组织进行转录组测序,并对与对照组相比的差异基因进行KEGG Pathway和GO功能富集分析;分析两种模型中共同的差异基因及其功能.结果:BAPN诱导的AD主要发生在胸主动脉,BAPN+Ang Ⅱ诱导的AD主要在腹主动脉,胸主动脉基本都有扩张,部分有夹层,EVG染色显示两种模型主动脉都存在弹力纤维的降解、断裂以及壁内血栓.转录组分析结果显示,两个模型中的上调基因均可富集出炎症、成骨细胞分化和细胞外基质等相关功能条目;2个模型中表达下调基因差异较大,BAPN组主要集中于免疫与脂质代谢方面,而BAPN+Ang Ⅱ组则以平滑肌细胞收缩相关基因富集最为显著.结论:两种AD模型的主动脉瘤和夹层形成部位存在差异,上调基因功能比较相似,下调基因差异较大,两种模型各有特点,可在应用中互补.
Abstract
Objective:To compare the transcriptomic characteristics of two experimental mouseaortic dissection models induced by β-aminoacetonitrile(BAPN)and BAPN combined with angiotensin Ⅱ(Ang Ⅱ).Methods:Thirty 3-week-old male C57BL/6J mice were randomly divided into two groups:Control group(Ctrl-1,n=10)and BAPN-induced AD group(BAPN,n=20).AD was induced by feeding the mice with diet containing 0.4％of BAPN for 3 weeks.Thirty 8 to 10-week-old male C57BL/6J mice were randomly divided into two groups:control group(Ctrl-1,n=10)and BAPN combined with Ang Ⅱ-induced AD group(BAPN+AngⅡ,n=20).AD was induced by Ang Ⅱ perfusion(1000 ng·kg-1·min-1)for 4 weeks with diet containing 0.15％of BAPN for the first two weeks.Images of the aortas from the two AD model mice were captured to analyze AD formation,and Verhoeff-Van Gieson staining was used to evaluate the degradation of elastic fibers.Transcriptome sequencing of aortic tissue from the two AD models was performed,and KEGG Pathway and Gene Ontology enrichment analysis was used to compare the function of differentially expressed genes(DEGs).Furthermore,the common DEGs in the two models and their functions were analyzed.Results:BAPN-induced AD predominantly occurred in the thoracic aorta,while BAPN+Ang Ⅱ induced AD mainly developed in the abdominal aorta with dilation of the thoracic aorta,and dissection in the thoracic aorta was observed in some mice.EVG staining showed degradation and fraction of elastic fibers and intramural thrombosis in the aortas of both models.The transcriptomic analysis showed that the upregulated gene in both models were enriched in the functional items related to inflammation,osteoblast differentiation,and extracellular matrix.However,the downregulated genes were quite different in the two models.The function of downregulated genes was related to immunity and lipid metabolism in BAPN group,and to smooth muscle cell contraction in BAPN+AngⅡ group.Conclusions:Dissection in BAPN-and BAPN combined with Ang Ⅱ-induced AD mouse models involve different aortic segments.The function of upregulated gene in both models was similar,but the downregulated genes varied.Both AD models have their own characteristics and can complement each other in application.
维普
万方数据