BACKGROUND The lncRNA NKILA has been reported to interact with NF-κB and has an important role in various human diseases. However, the role of NKILA in myocardial ischaemic injury is still unknown. METHODS We established cell and animal models of myocardial ischaemic injury. We confirmed our findings by overexpressing NKILA, silencing myocardin and using an NF-κB pathway inhibitor in a hypoxia/reoxygenation (H/R) model of H9c2 cells. An animal model of ischaemia-reperfusion (I/R) injury was established by LAD ligation. Overexpression of NKILA was achieved by adeno-associated virus (AAV) injection through the tail vein. Annexin-V/PI staining and flow cytometric analysis were performed to test cell apoptosis. ELISAs were used to determine the secretion of inflammatory factors. TTC, HE and TUNEL staining were performed to study myocardial pathological injury. qRT-PCR or Western blotting were used to test the expression levels of NKILA, myocardin, the NF-κB pathway and apoptosis-related proteins. RESULTS H/R and I/R treatment significantly suppressed the expression of NKILA and activated the NF-κB pathway, resulting in the loss of myocardin. Overexpressing NKILA led to the suppression of the NF-κB pathway and successfully prevented the cell apoptosis and inflammatory responses caused by H/R stimulation in H9c2 cells. Silencing myocardin reversed the protective effect of NKILA and led to severe injury in the H9c2 cells that underwent H/R. Furthermore, the NF-κB pathway inhibitor BAY11-7028 reduced the H/R injury in H9c2 cells with little effect on NKILA expression. Similar results were confirmed in an animal model of myocardial I/R injury and showed that overexpression of NKILA inhibited I/R-triggered myocardial injury in vivo. CONCLUSION NKILA enhanced the expression of myocardin via inhibiting the NF-κB signalling pathway and preventing cell apoptosis and the inflammatory response of cardiomyocytes, thus ameliorating myocardial I/R injury.

中文翻译：

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较长的非编码RNA NKILA通过抑制NF-κB信号通路来增强心肌蛋白的表达，从而预防心肌缺血。

背景技术据报道，lncRNA NKILA与NF-κB相互作用，并且在各种人类疾病中具有重要作用。但是，NKILA在心肌缺血性损伤中的作用仍是未知的。方法我们建立了心肌缺血性损伤的细胞和动物模型。我们通过在H9c2细胞的低氧/复氧（H / R）模型中过表达NKILA，沉默心肌素和使用NF-κB途径抑制剂来证实我们的发现。通过LAD结扎建立了缺血再灌注（I / R）损伤的动物模型。NKILA的过表达是通过通过尾静脉注射腺相关病毒（AAV）来实现的。进行膜联蛋白-V / PI染色和流式细胞仪分析以测试细胞凋亡。ELISA用于确定炎性因子的分泌。TTC，进行HE和TUNEL染色以研究心肌病理损伤。采用qRT-PCR或Western blotting检测NKILA，心肌蛋白，NF-κB途径和凋亡相关蛋白的表达水平。结果H / R和I / R处理可显着抑制NKILA的表达并激活NF-κB通路，从而导致心肌素的丢失。NKILA的过表达导致NF-κB通路的抑制，并成功地阻止了H9c2细胞中H / R刺激引起的细胞凋亡和炎症反应。沉默心肌素会逆转NKILA的保护作用，并导致接受H / R的H9c2细胞受到严重伤害。此外，NF-κB途径抑制剂BAY11-7028减少了H9c2细胞的H / R损伤，而对NKILA表达的影响很小。在心肌I / R损伤的动物模型中证实了类似的结果，并表明NKILA的过表达在体内抑制了I / R触发的心肌损伤。结论NKILA通过抑制NF-κB信号通路，阻止细胞凋亡和心肌细胞的炎症反应来增强心肌的表达，从而减轻心肌I / R损伤。