Emodin alleviates myocardial ischemia/reperfusion injury by inhibiting gasdermin D-mediated pyroptosis in cardiomyocytes
Emodin alleviates myocardial ischemia/reperfusion injury by inhibiting gasdermin D-mediated pyroptosis in cardiomyocytes
复制标题
大黄素通过抑制gasdermin D介导的心肌细胞焦亡减轻心肌缺血/再灌注损伤
DOI：
10.2147/dddt.s195412
复制
发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Huang, Weijian
中科院分区：
文献类型：
--
作者：
Ye, Bozhi;Chen, Xudong;Huang, Weijian
工作背景：大黄素具有很强的抗心肌缺血再灌注（I/R）损伤作用。Pyroptosis是一种促炎症程序性细胞死亡，与许多疾病相关。材料与方法：道利大鼠随机分为假手术组、缺血再灌注组和缺血再灌注+大黄素组。结扎冠状动脉左前降支30 min，再灌注2 h。将心肌细胞暴露于低氧条件1小时和常氧条件2小时。结果：心肌细胞Gasdermin D-N结构域在I/R或缺氧/复氧（H/R）处理过程中表达上调。此外，大黄素通过抑制I/R诱导的细胞凋亡水平，增加体外细胞存活率，减少体内心肌梗死面积。此外，TLR 4，MyD 88，磷酸化-I κ B α，磷酸化-NF-κ B，和NLRP 3炎性体的表达在心肌细胞受到H/R treatment.Conclusion的，而大黄素抑制这些蛋白的表达，本研究证实，大黄素治疗能够减轻心肌I/R损伤，抑制pyroptosis在体内和体外。大黄素通过抑制TLR 4/MyD 88/NF-κ B B/NLRP 3炎症体通路抑制细胞凋亡。因此，大黄素可能为心肌I/R损伤提供一种替代治疗方法。
Background: Emodin has recently been reported to have a powerful antiinflammatory effect, protecting the myocardium against ischemia/reperfusion (I/R) injury. Pyroptosis is a proinflammatory programmed cell death that is related to many diseases. The present study investigated the effect of emodin on pyroptosis in cardiomyocytes.Materials and methods: Sprague Dawley rats were randomly divided into sham, I/R, and I/R+Emodin groups. I/R model was subjected to 30 minutes' ligation of left anterior descending coronary artery, followed by 2 hours of reperfusion. Cardiomyocytes were exposed to hypoxic conditions for 1 hour and normoxic conditions for 2 hours. The level of the pyroptosis was detected by Western blot, real-time PCR analysis, and ELISA.Results: The level of gasdermin D-N domains was upregulated in cardiomyocytes during I/R or hypoxia/reoxygenation (H/R) treatment. Moreover, emodin increased the rate of cell survival in vitro and decreased the myocardial infarct size in vivo via suppressing the levels of I/R-induced pyroptosis. Additionally, the expression of TLR4, MyD88, phospho-I kappa B alpha, phospho-NF-kappa B, and the NLRP3 inflammasome was significantly upregulated in cardiomyocytes subjected to H/R treatment, while emodin suppressed the expression of these proteins.Conclusion: This study confirms that emodin treatment was able to alleviate myocardial I/R injury and inhibit pyroptosis in vivo and in vitro. The inhibitory effect of emodin on pyroptosis was mediated by suppressing the TLR4/MyD88/NF-kappa B/NLRP3 inflammasome pathway. Therefore, emodin may provide an alternative treatment for myocardial I/R injury.