Effect of emodin on long non-coding RNA-mRNA networks in rats with severe acute pancreatitis-induced acute lung injury

Long non-coding RNAs (lncRNAs) reportedly contribute to disease pathogenesis and drug treatment effects. Both emodin and dexamethasone (DEX) have been used for the treatment of severe acute pancreatitis-associated acute lung injury (SAP-ALI). However, lncRNA regulation networks related to SAP-ALI pathogenesis and drug treatment are unreported. In this study, lncRNAs and mRNAs in the lung tissue of SAP-ALI and control rats, with or without drug treatment (emodin or DEX), were assessed by RNA sequencing. Results showed that both emodin and DEX were therapeutic for SAP-ALI and that mRNA and lncRNA levels differed between untreated and treated SAP-ALI rats. Gene expression profile relationships for emodin treated and control rats were higher than DEX treated and untreated animals. By comparison of control and SAP-ALI animals, more upregulated than downregulated mRNAs and lncRNAs were observed with emodin treatment. For DEX treatment, more downregulated than upregulated mRNAs and lncRNAs were observed. Functional analysis demonstrated both upregulated mRNA and co-expressed genes with upregulated lncRNAs were enriched in inflammatory and immune response pathways. Further, emodin associated lncRNAs and mRNAs co-expressed modules were different from those associated with DEX. Quantitative polymerase chain reaction demonstrates that selected lncRNA and mRNA co-expressed modules were different in the lung tissue of emodin and DEX treated rats. Also, emodin had different effects compared to DEX on the co-expression network of lncRNAs Rn60_7_1164.1 and AABR07062477.2 for the blue lncRNA module and Nrp1 for the green mRNA module. In conclusion, this study provides evidence that emodin may be a suitable alternative or complementary medicine for treatment of SAP-ALI.据报道，长链非编码RNA（long non-coding RNAs，lncRNAs）参与疾病发病机制与药物治疗效应。大黄素与地塞米松（dexamethasone，DEX）均已用于重症急性胰腺炎相关性急性肺损伤（severe acute pancreatitis-associated acute lung injury，SAP-ALI）的治疗。然而，与SAP-ALI发病机制及药物治疗相关的lncRNA调控网络迄今尚未见报道。本研究通过RNA测序（RNA sequencing）技术，对接受或未接受药物治疗（大黄素或DEX）的SAP-ALI模型大鼠及对照大鼠的肺组织中lncRNAs与mRNA（messenger RNA）的表达水平进行了检测。结果显示，大黄素与DEX均对SAP-ALI具有治疗作用，且未给药与给药的SAP-ALI大鼠的mRNA及lncRNA表达水平存在差异。大黄素处理组大鼠与对照组大鼠的基因表达谱相关性高于DEX处理组与未给药组大鼠。通过对比对照组与SAP-ALI模型组大鼠，经大黄素处理后，上调的mRNA与lncRNA数量多于下调者；而经DEX处理后，下调的mRNA与lncRNA数量多于上调者。功能富集分析显示，上调的mRNA及与上调lncRNA共表达的基因均富集于炎症与免疫应答通路。此外，与大黄素相关的lncRNA与mRNA共表达模块，与DEX相关的模块存在显著差异。定量聚合酶链反应（quantitative polymerase chain reaction）验证结果显示，筛选得到的lncRNA与mRNA共表达模块在大黄素处理组与DEX处理组大鼠的肺组织中存在表达差异。此外，相较于DEX，大黄素对蓝色lncRNA模块中的lncRNA Rn60_7_1164.1与AABR07062477.2，以及绿色mRNA模块中的Nrp1的共表达网络具有不同的调控作用。综上，本研究证实大黄素可作为SAP-ALI治疗的合适替代或辅助治疗药物。