期刊
DRUG DESIGN DEVELOPMENT AND THERAPY
卷 13, 期 -, 页码 975-990出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S195412
关键词
emodin; ischemia/reperfusion injury; gasdermin D; pyroptosis; heart
资金
- Cardiac Rehabilitation and Metabolic Therapy Research Fund
- National Natural Science Foundation of China [81670227]
- Natural Science Foundation of Zhejiang Province [LQ19H020004]
- Traditional Chinese Medicine Administration of Zhejiang Province [2016ZA137]
- Wenzhou Science and Technology Bureau [Y20170045, Y20160030, Y20180105]
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.
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