期刊
INFLAMMATION RESEARCH
卷 71, 期 2, 页码 227-241出版社
SPRINGER BASEL AG
DOI: 10.1007/s00011-021-01530-6
关键词
Trimetazidine; Ischemia; reperfusion injury; GSDMD; Pyroptosis; Heart
资金
- National Natural Science Foundation of China [81670227, 81600341]
- Natural Science Foundation of Zhejiang Province [LQ19H020004]
- Cardiac Rehabilitation and Metabolic Therapy research fund [2019ZJXQN03]
- Medical Health Science and Technology Project of Zhejiang Provincial [2021KY1072]
- Wenzhou Science and Technology Bureau [Y20170045, Y20160030, Y20180105]
- Traditional Chinese Medicine Administration of Zhejiang Province [2016ZA137]
Trimetazidine can protect cardiomyocytes from ischemia/reperfusion injury by inhibiting inflammation. This research is of great significance for the development of alternative treatments for myocardial I/R injury.
Objective Trimetazidine (TMZ) exerts a strong inhibitory effect on ischemia/reperfusion (I/R) injury. Inflammation plays a key role in I/R injury. We hypothesized that TMZ may protect cardiomyocytes from I/R injury by inhibiting inflammation. Methods The left anterior descending coronary artery was ligated for 30 min followed by 6 h of reperfusion to establish a model of I/R injury. H9c2 cardiomyocytes were subjected to 2 h of hypoxia and 3 h of normoxic conditions to establish a model of hypoxia/reoxygenation (H/R) injury. We monitored the change in pyroptosis by performing Western blot analysis, microscopy and ELISA. Results I/R and H/R treatment stimulated gasdermin D-N domain (GSDMD-N) expression in cardiomyocytes (sham onefold vs. I/R 2.5-fold; control onefold vs. H/R 2.0-fold). Moreover, TMZ increased the viability of H9c2 cardiomyocytes subjected to H/R treatment (H/R 65.0% vs. H/R + TMZ 85.3%) and reduced the infarct size in vivo (I/R 47.0% vs. I/R + TMZ 28.3%). H/R and I/R treatment increased the levels of TLR4, MyD88, phospho-NF-kappa B p65 and the NLRP3 inflammasome; however, TMZ reduced the expression of these proteins. Additionally, TMZ inhibited noncanonical inflammasome signaling induced by I/R injury. Conclusions In summary, TMZ alleviated pyroptosis induced by myocardial I/R injury through the TLR4/MyD88/NF-kappa B/NLRP3 inflammasome pathway. Therefore, TMZ represents an alternative treatment for myocardial I/R injury.
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