摘要
目的:探讨丹红注射液(DHI)对急性心肌梗死(AMI)模型大鼠基因表达谱的影响。方法:将雄性SD大鼠随机分为假手术组、模型组和DHI组(0.76 mL/kg),每组10只。模型组和DHI组采用冠状动脉左前降支结扎法复制AMI模型。造模后,假手术组和模型组大鼠均肌内注射等容生理盐水,DHI组大鼠肌内注射相应药物,每日1次,连续14 d。末次给药后,分离大鼠梗死边缘区心肌组织,采用基因芯片技术检测基因表达谱的变化情况,以相对表达量差异倍数为指标,筛选差异表达微RNA(miRNA)。在检索其对应基因的基础上,利用DAVID生物信息学资源数据库和KEGG通路数据库分别进行基因本体(GO)和KEGG通路富集分析;借助TargetScan数据库预测差异表达miRNA对应的靶基因信使RNA(mRNA),采用Cytoscape 3.6.1软件构建miRNAmRNA网络并进行分析,采用Agilent GeneSpring GX v11.5软件筛选上述网络中与炎症相关的靶基因和miRNA。结果:与假手术组比较,模型组差异表达miRNA共22个,其中上调5个、下调17个;与模型组比较,DHI组差异表达miRNA共26个,均为上调;与DHI治疗AMI有关的差异表达miRNA包括rno-let-7a-5p、rno-let-7d-5p、rno-let-7f-5p、rno-miR-26b-5p、rno-miR-29b-3p、cel-miR-39-3p、cel-miR-39-5p、rno-miR-142-5p、rno-miR-191a-5p、rno-miR-409a-3p。GO和KEGG通路富集分析结果显示,差异表达miRNA对应基因主要集中在膜结合细胞器、细胞质、内膜系统等细胞组分中,通过解剖结构发育、多细胞组织发育、发育过程等生物过程来发挥蛋白结合、离子结合等分子功能;其主要富集于钙信号通路,过氧化物酶体增殖物激活受体(PPAR)信号通路,血管内皮生长因子(VEGF)信号通路,细胞凋亡,糖基磷脂酰肌醇锚定生物合成,缬氨酸、亮氨酸和异亮氨酸降解等信号通路上。miRNA-mRNA网络分析结果显示,与差异表达miRNA对应的靶基因mRNA共25个,与之关联的miRNA共24个;该网络中与炎症相关的靶基�
OBJECTIVE:To investigate the effects of Danhong injection(DHI)on gene expression profile of acute myocardial infarction(AMI)model rats.METHODS:Male SD rats were randomly divided into sham operation group,model group and DHI group(0.76 mL/kg),with 10 rats in each group.AMI model was established by ligation of left anterior descending coronary artery in model group and DHI group.After modeling,sham operation group and model group were given constant volume of normal saline intramuscularly,and DHI group was given relevant medicine intramuscularly,once a day,for consecutive 14 days.After last administration,myocardial tissue in the marginal zone of infarction was separated.The change of gene expression profile was detected by gene chip technique.Using fold-change of relative expression as index,differentially expressed microRNA(miRNA)were screened.On the basis of retrieving their corresponding genes,gene ontology(GO)and KEGG pathway enrichment analysis were carried out by using DAVID bioinformatics resource database and KEGG pathway database,respectively.TargetScan database was used to predict the target gene messenger RNA(mRNA)corresponding to differentially expressed miRNA.Cytoscape 3.6.1 software was used to construct and analyze the miRNA-mRNA network.Agilent GeneSpring GX v11.5 software was used to screen target genes and miRNA related to inflammation in the above networks.RESULTS:Compared with sham operation group,there were 22 differentially expressed miRNAs in model group,5 up-regulated and 17 down-regulated.Compared with model group,there were 26 differentially expressed miRNAs in DHI group,and all of them were up-regulated.The differentially expressed miRNAs related to DHI therapy for AMI included rno-let-7a-5p,rno-let-7d-5p,rno-let-7f-5p,rno-miR-26b-5p,rno-miR-29b-3p,cel-miR-39-3p,cel-miR-39-5p,rno-miR-142-5p,rno-miR-191a-5p,rno-miR-409a-3p.Results of GO analysis and KEGG pathway enrichment analysis showed that differentially expressed miRNAs were mainly concentrated in membrane-bound organelles,cytoplasm,
作者
施洋
樊官伟
候宝林
樊登峰
张伟
鲁西亮
陈晓黎
何敏
SHI Yang;FAN Guanwei;HOU Baolin;FAN Dengfeng;ZHANG Wei;LU Xiliang;CHEN Xiaoli;HE Min(Dept.of Pharmacy,Karamay Municipal People’s Hospital,Xinjiang Karamay 834000,China;Dept.of Pharmacy,Karamay Hospital of TCM,Xinjiang Karamay 834000,China;Tianjin Key Laboratory of Modern Chinese Medicine/State Key Lab Breeding Base,Tianjin 300193,China;Medical Experiment Center,the First Affiliated Hospital of Tianjin University of TCM,Tianjin 300193,China)
出处
《中国药房》
CAS
北大核心
2019年第22期3042-3048,共7页
China Pharmacy
基金
国家自然科学基金资助项目（No.81774050）
天津市杰出青年科学基金资助项目（No.17JCJQJC46200）
克拉玛依市人民医院院级科研项目（No.Ry2018014）
关键词
基因芯片技术
丹红注射液
急性心肌梗死
差异表达
微RNA
信使RNA
信号通路
炎症
大鼠
Gene chip technique
Danhong injection
Acute myocardial infarction
Differential expression
MicroRNA
Messenger RNA
Signaling pathway
Inflammation
Rat
