BACKGROUND Activation of NLRP3 inflammasome plays a key role in cardiac dysfunction for acute myocardial ischemia-reperfusion injury. Scutellarin (Scu) is a flavonoid purified from Erigeron breviscapus. Whether Scu has any influence on the activation of NLRP3 inflammasome in cardiomyocytes remains unknown. PURPOSE We aimed to examine the therapeutic effect of Scu on cardiomyocyte ischemia-reperfusion (I/R) injury and its effect on NLRP3 inflammasome in rats with acute myocardial I/R injury and anoxia/reoxygenation (A/R)-induced H9c2 injuries. METHODS Heart injuries were induced through 30 min of ischemia followed by 24 h of reperfusion. Scu was intraperitoneally administered 15 min before vascular ligation. Effects of Scu on cardiac injury were detected by echocardiograms, TTC staining, and histological and immunohistochemical analyses. The effects of Scu on biochemical parameters were analyzed. H9c2 cells were pretreated with different concentrations of Scu for 6 h before A/R exposure. Afterward, cell viability, LDH release, and Hoechst 33342 and peromide iodine double staining were determined. Western blot analyses of proteins, including those involved in autophagy, NLRP3, mTOR complex 1 (mTORC1), and Akt signaling, were conducted. RESULTS In vivo study revealed that Scu improved diastolic dysfunction, ameliorated myocardium structure abnormality, inhibited myocyte apoptosis and inflammatory response, and promoted autophagy. Scu reduced NLRP3 inflammasome activation, inhibited mTORC1 activity, and increased Akt phosphorylation. In vitro investigation showed the same results. The Scu-mediated NLRP3 inflammasome and mTORC1 inhibition and cardioprotection were abolished through the genetic silencing of Akt by siRNA. CONCLUSIONS The cardioprotective effect of Scu was achieved through its anti-inflammatory effect. It suppressed the activation of NLRP3 inflammasome. In addition, inflammasome restriction by Scu was dependent on Akt activation and mTORC1 inhibition.

中文翻译：

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黄cut素可通过抑制NLRP3炎性体激活来保护心肌免于缺血再灌注损伤。

背景技术NLRP3炎性体的激活在急性心肌缺血-再灌注损伤的心脏功能障碍中起关键作用。黄cut苷（Scu）是从灯盏花中提取的黄酮。Scu是否对心肌细胞中NLRP3炎性小体的活化有任何影响尚不清楚。目的我们旨在研究Scu对急性心肌I / R损伤和缺氧/复氧（A / R）诱导的H9c2损伤大鼠心肌缺血再灌注（I / R）损伤的治疗作用及其对NLRP3炎性体的作用。方法缺血30分钟后再灌注24 h诱发心脏损伤。血管结扎前15分钟腹腔注射Scu。通过超声心动图，TTC染色以及组织学和免疫组化分析检测Scu对心脏损伤的影响。分析了Scu对生化参数的影响。在A / R暴露之前，将H9c2细胞用不同浓度的Scu预处理6小时。然后，测定细胞活力，LDH释放，Hoechst 33342和碘化物碘双染。对蛋白质进行了蛋白质印迹分析，包括与自噬，NLRP3，mTOR复合物1（mTORC1）和Akt信号转导有关的蛋白质。结果体内研究表明，Scu可改善舒张功能障碍，改善心肌结构异常，抑制心肌细胞凋亡和炎症反应并促进自噬。Scu减少了NLRP3炎性体的激活，抑制了mTORC1的活性，并增加了Akt的磷酸化。体外调查显示相同的结果。Scu介导的NLRP3炎性小体和mTORC1抑制和心脏保护通过siRNA的Akt遗传沉默而被取消。结论Scu的抗炎作用是通过其心脏保护作用实现的。它抑制了NLRP3炎性小体的激活。此外，Scu对炎性体的限制还取决于Akt激活和mTORC1抑制。