参附注射液对慢性充血性心力衰竭大鼠心肌miRNA表达谱的影响
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篇名: 参附注射液对慢性充血性心力衰竭大鼠心肌miRNA表达谱的影响
TITLE:
摘要: 目的:研究参附注射液(SFI)对慢性充血性心力衰竭(简称心衰)大鼠心肌微小RNA(miRNA)表达谱的影响,以明确SFI抗心衰的作用靶点。方法:将40只大鼠按随机数字表法分成假手术组(生理盐水,ip)、模型组(生理盐水,ip)、缬沙坦组(阳性对照,10 mg/kg,ig)和SFI组(0.75 mL/kg,im),每组10只,除假手术外的其余各组大鼠均复制心衰模型。造模成功后,各组小鼠每天给予相应药物1次,连续给药28 d后采用Affymetrix miRNA V4.0芯片技术对心衰大鼠心肌组织中miRNA表达进行分析,并筛选各组大鼠心肌组织中共同差异表达miRNA,以差异基因表达倍数大于或等于1.1为阈值分析心衰相关miRNA;利用基因本体论(GO)分析对差异表达基因进行功能分类及生物信号通路分析。结果:共筛选出29条共同差异表达miRNA,7条心衰相关miRNA(rno-miR-30c-1-3p、rno-miR-125b-5p、rno-miR-133a-5p、rno-miR-199a-5p、rno-miR-221-3p、rno-miR-146a-5p和rno-miR-1-3p),SFI能显著下调心衰大鼠心肌组织中rno-miR-125b-5p、rno-miR-133a-5p、rno-miR-221-3p、rno-miR-1-3p表达(P<0.05或P<0.01)。GO分析结果显示,差异表达miRNA主要与信号通路转导、细胞质及核苷酸结合有关。结论:SFI参与下调心衰进展相关miRNA,进而经细胞质与核苷酸结合后影响相关信号通路的转导,从而发挥其抗心衰作用。
ABSTRACT: OBJECTIVE: To study the effect of Shenfu injection (SFI) on the expression profile of myocardial miRNA in rats with chronic congestive heart failure (referring to heart failure). METHODS: 40 rats were randomly divided into sham operation group (normal saline, ip), model group (normal saline, ip), valsartan group (positive control, 10 mg/kg, ig) and SFI group (0.75 mL/kg, im), 10 in each group. Except for sham operation group, another groups were reduced heart failure. After modeling, rats in other groups received related medicines, once a day. Affymetrix miRNA V4.0 chip technology was conducted to analyze the miRNA expression in myocardial tissue of rats with heart failure after administration for 28 d, and screen the miRNA on common differential expression in myocardial tissue of rats in each group. The miRNA associated with heart failure was analyzed by threshold of differential gene expression multiple value greater than or equal to 1.1. Gene Ontology (GO) analysis was used to analyze functional classification and biological signaling pathway of differentially expressed genes. RESULTS: There were totally 29 miRNAs on common differential expression and 7 miRNAs associated with heart failure (rno-miR-30c-1-3p, rno-miR-125b-5p, rno-miR-133a-5p, rno-miR-199a-5p, rno-miR-221-3p, rno-miR-146a-5p and rno-miR-1-3p). SFI can significantly downregulate the expressions of rno-miR-125b-5p, rno-miR-133a-5p, rno-miR-221-3p, rno-miR-1-3p in myocardial tissue of rats (P<0.05 or P<0.01). Results of GO analysis showed, miRNAs on differential expression were mainly related to signal transduction, cytoplasm and nucleotide binding. CONCLUSIONS: SFI plays the role of anti-heart failure by participating in the downregulation of miRNAs associated with heart failure process and then affecting related signal pathways transduction after the combination of cytoplasm and nucleotide.
期刊: 2017年第28卷第22期
作者: 施洋,樊官伟
AUTHORS: SHI Yang,FAN Guanwei
关键字: 参附注射液;慢性充血性心力衰竭;微小RNA;差异筛选;基因本体论分析
KEYWORDS: Shenfu injection; Chronic congestive heart failure; miRNA; Differential screening; Gene ontology analysis
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