摘要
目的研究血管紧张素Ⅱ(AngⅡ)诱导的大鼠纤维化心肌细胞与正常大鼠心肌细胞mRNA表达谱之间的差异及其相关信号通路。方法8周龄雄性SD大鼠6只,随机分为对照组(Control组)和AngⅡ组,每组3只。Control组每日经尾静脉注射生理盐水,AngⅡ组则注射2 mg/kg的AngⅡ,两组持续给药14 d。采用Masson染色法检测大鼠心肌纤维化程度,免疫组化法检测胶原蛋白Ⅰ含量。利用高通量测序技术检测两组大鼠心肌细胞mRNA的表达并筛选出差异mRNA,进行GO分析和KEGG通路分析。结果与Control组相比,AngⅡ组的心肌纤维化程度及胶原蛋白Ⅰ含量升高(P<0.05)。进行测序后共筛选出313条差异mRNA(其中201条上调,112条下调)。GO和KEGG分析表明上述差异表达的mRNA参与了心肌纤维化的多种生物学调节功能和通路。结论AngⅡ可以导致大鼠心肌发生纤维化;纤维化的心肌细胞与正常心肌细胞之间的mRNA表达具有明显差异,差异表达的mRNA在免疫反应、细胞重构、细胞外基质沉积等生物过程中可能发挥重要作用。
Objective To study the differences between the mRNA expression profile in angiotensinⅡ(AngⅡ)-induced fibrotic cardiomyocytes and that of normal cardiomyocytes and the relevant signaling pathways.Methods Six 8-week-old male Sprague-Dawley(SD)rats were randomly assigned to a control group and an AngⅡgroup,with 3 rats in each group.Rats in the control group were injected via caudal vein with 0.9%normal saline at 2 mg/kg per day,while rats in the AngⅡgroup were injected with AngⅡvia caudal vein at 2 mg/kg per day.The medications were continuously administered in the two groups for 14 days.The degree of myocardial fibrosis was determined by Masson's Trichrome staining and the content of collagenⅠwas determined by immunohistochemistry.High throughput sequencing was performed to measure the mRNA expression of rat cardiomyocytes in the two groups and to screen for differentially-expressed mRNAs.The differentially-expressed mRNAs were analyzed by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Results Compared with those of the control group,the degree of myocardial fibrosis and the content of collagenⅠin AngⅡgroup were significantly higher(P<0.05).Through sequencing,313 differentially-expressed mRNAs were identified,with 201 being up-regulated and 112 being down-regulated.Go and KEGG analyses showed that these differentially-expressed mRNA were involved in a variety of biological regulatory functions and pathways of myocardial fibrosis.Conclusion AngⅡcan cause myocardial fibrosis in rats.There are significant differences in mRNA expression between fibrotic cardiomyocytes and normal cardiomyocytes.The differentially expressed mRNAs may play an important role in biological processes,including immune response,cell remodeling,and extracellular matrix deposition.
作者
覃秋语
吕祥威
何梓峰
陈礼琴
路凤霞
李于庭
黄宇莉
莫琪
徐华欣
吕菲
QIN Qiuyu;LYU Xiangwei;HE Zifeng;CHEN Liqin;LU Fengxia;LI Yuting;HUANG Yuli;MO Qi;XU Huaxin;LYU Fei(Department of Medical Care Ward,Affiliated Hospital of Guilin Medical University,Guilin 541001,China;Department of Development Planning and Hospital Management,Guilin Medical University,Guilin 541199,China;Guilin Medical University,Guilin 541199,China;Department of Organization,Affiliated Hospital of Guilin Medical University,Guilin 541001,China)
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2023年第5期959-964,共6页
Journal of Sichuan University(Medical Sciences)
基金
国家自然科学基金地区项目(No.82160068)
国家级大学生创新创业训练计划项目资助(No.202110601004)资助。
