Long non-coding RNA and mRNA expression profiles in rats with LPS-induced myocardial dysfunction

Sepsis is a life-threatening disease that often causes multiple organ dysfunctions. Long noncoding RNAs (lncRNAs) are involved in the pathogenesis and development of sepsis. However, there is little known about the function of lncRNAs in sepsis-induced myocardial dysfunction.To test the hypothesis that dysregulating lncRNAs may be involved in sepsis-induced myocardial dysfunction, we identified differentially expressed (DE) lncRNAs and mRNAs in cardiac tissue by high-throughput sequencing. We constructed coding and non-coding co-expression (CNC) and lncRNA-micro RNA (miRNA)-mRNA competing endogenous networks. The findings will provide useful information for exploring therapeutic candidate targets and new molecular biomarkers of septic myocardial injury. Male Wistar rats (8–10 weeks old, 150–200 g) were randomly divided into the following two groups: rats in the LPS group (n = 5) received an intraperitoneal injection of 10mg/kg LPS (5 mg LPS dissolved in 1 mL 0.9% saline), and those in the control group (n = 5) were intraperitoneally injected with 0.9% saline (2 ml/kg). we analyzed the lncRNAs, miRNAs and mRNAs expression profiles using RNA-seq. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were carried out and coding and non-coding co-expression and competing endogenous RNA networks were constructed to investigate the mechanisms.

脓毒症（Sepsis）是一种危及生命的疾病，常引发多器官功能障碍。长链非编码RNA（long noncoding RNAs, lncRNAs）参与了脓毒症的发病机制与病程进展，然而目前对于长链非编码RNA在脓毒症诱导心肌功能障碍中的作用仍知之甚少。为验证“长链非编码RNA表达失调可能参与脓毒症诱导心肌功能障碍”这一假说，我们通过高通量测序技术鉴定了心肌组织中的差异表达（differentially expressed, DE）长链非编码RNA与信使RNA（mRNA）。我们构建了编码-非编码共表达（coding and non-coding co-expression, CNC）网络以及长链非编码RNA-微小RNA（micro RNA, miRNA）-信使RNA内源竞争RNA网络。本研究结果可为脓毒症心肌损伤的治疗候选靶点与新型分子生物标志物的探索提供有价值的参考依据。选取8~10周龄、体重150~200g的雄性Wistar大鼠，随机分为两组：脂多糖（lipopolysaccharide, LPS）组（n=5）大鼠经腹腔注射10mg/kg脂多糖（将5mg脂多糖溶解于1mL 0.9%生理盐水中），对照组（n=5）大鼠经腹腔注射0.9%生理盐水（2ml/kg）。我们通过RNA测序（RNA-seq）技术分析了长链非编码RNA、微小RNA与信使RNA的表达谱，并开展了基因本体论（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析，同时构建编码-非编码共表达网络与内源竞争RNA网络以探究其潜在作用机制。