Scutellarin protects against myocardial ischemia-reperfusion injury by suppressing NLRP3 inflammasome activation
Scutellarin protects against myocardial ischemia-reperfusion injury by suppressing NLRP3 inflammasome activation
复制标题
灯盏花乙素通过抑制 NLRP3 炎性体激活来预防心肌缺血再灌注损伤
DOI：
10.1016/j.phymed.2020.153169
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发表时间：
2020-03-01
期刊：
影响因子：
7.9
通讯作者：
Sun, Xiao-bo
中科院分区：
文献类型：
--
作者：
Xu, Li-jiao;Chen, Rong-chang;Sun, Xiao-bo
背景：NLRP 3炎性体的激活在急性心肌缺血再灌注损伤的心功能障碍中起关键作用。灯盏乙素（Scu）是从灯盏花（Erigeron breviscapus）中分离得到的一种黄酮类化合物。Scu是否对心肌细胞中NLRP 3炎性体的活化有任何影响尚不清楚。目的：我们旨在检测Scu对心肌细胞缺血再灌注（I/R）损伤的治疗作用及其对急性心肌I/R损伤和缺氧/复氧（A/R）诱导的H9 c2损伤的大鼠中NLRP 3炎性体的影响。通过30分钟的缺血再灌注24小时诱导心脏损伤。血管结扎前15 min腹腔注射Scu。通过超声心动图、TTC染色、组织学和免疫组化观察Scu对心肌损伤的影响。分析了Scu对生化指标的影响。在A/R暴露前用不同浓度的Scu预处理H9 c2细胞6 h。然后，测定细胞活力、LDH释放以及Hoechst 33342和peromide碘双染色。结果：在体研究表明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，促进自噬。Scu减少NLRP 3炎性小体激活，抑制mTORC 1活性，并增加Akt磷酸化。体外研究显示了相同的结果。Scu通过siRNA沉默Akt基因表达，可抑制NLRP 3和mTORC 1对心肌的抑制作用。结论：Scu的心肌保护作用是通过抗炎作用实现的。抑制NLRP 3炎性小体的活化。此外，Scu对炎性小体的限制依赖于Akt激活和mTORC 1抑制。
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.