姜黄素对压力超负荷大鼠左心房微小RNA表达谱的影响

Effects of Curcumin on Expression Profile of Micro RNA Extracted from Left Atria of Pressure-Overload Rats

目的探讨姜黄素对压力超负荷大鼠纤维化左心房组织微小RNA(miRNA)表达谱的影响。方法45只雄性SD大鼠按照随机数字表法分为对照组(n=15)、模型组(n=15)和姜黄素组(n=15)。制备0.7 mm腹主动脉缩窄(AAC)模型,对照组不进行AAC,姜黄素组AAC术后接受300 mg/(kg·d)姜黄素连续灌胃4周。4周时提取大鼠左心房总RNA,通过高通量测序筛选3组间显著差异表达的mRNA和miRNA;通过基因本体(GO)和京都基因和基因组数据库(KEGG)富集分析、蛋白互作网络(PPI)和miRNA-mRNA关联分析,确定相关的miRNA靶点。结果基因测序和生信分析显示,符合模型组下调+姜黄素组上调的miRNA 155个,符合模型组上调+姜黄素组下调的miRNA 224个。KEGG/GO富集分析和PPI分析、miRNA-mRNA关联分析,共筛选出目标miRNA 9个,分别为rno-miR-667-3p、rno-miR-93-3p、rno-miR-30c-1-3p、rno-miR-329-5p、rno-miR-296-3p、rno-miR-150-5p、rno-miR-330-5p和rno-miR-3068-5p、rno-miR-17-5p;其中rno-miR-150-5p为表达量最大和组间差异最显著的关键miRNA靶点。结论姜黄素通过调控以miR-150-5p为主的系列miRNA异常表达,改善了压力超负荷高血压大鼠左心房纤维化及房颤易感性。

Objective To explore the effects of curcumin on expression profile of microRNA originated from fibrotic left atria of pressure-overload rats.Methods Forty-five 12-week-old male SD rats were randomly divided into control group(n=15),abdominal aorta constriction(AAC)model group(model group,n=15)and curcumin group(n=15)by random number table.The AAC model was established using 0.7 mm diameter needles in model group and curcumin group,while rats in the control group was not given AAC.Rats in the curcumin group were given curcumin 300 mg·kg~(-1)·d~(-1)by gavage for 4 weeks after AAC.Four weeks over operation,the total RNA(including mRNA and miRNA)extracted from left atrial tissues of the above 3 groups were quantified with high throughput sequencing,through which differently expressed genes were selected.Then hug genes were identified and defined in terms of Kyoto Encyclopedia of Genes and Genomes(KEGG),Gene Ontology(GO)enrichment,protein-to-protein interact(PPI)and miRNA-mRNA correlation analysis.Results MiRNAs which down-regulated in model group in concurrent with up-regulation in curcumin group were collected up to 155,while up-regulated in model group in combination with down-regulation in curcumin group were summarized up to 224.In terms of KEGG/GO enrichment analysis,PPI analysis and miRNA-mRNA correlation analysis,9target miRNAs namely rno-miR-667-3p,rno-miR-93-3p,rno-miR-30c-1-3p,rno-miR-329-5p,rno-miR-296-3p,rno-miR-150-5p,rno-miR-330-5p,rno-miR-3068-5p and rno-miR-17-5p were screened.Finally rno-miR-150-5p was defined as the hug miRNA characterized by it's maximum expression and largest expression difference.Conclusions Effects of Curcumin on improvement in left atrial remodeling and atrial fibrillation susceptibility are associated with it's impacts on expression of miRNA series characterized with miR-150-5p.