科研之友
微信
新浪微博
Facebook
分享链接
摘要
Inflammation serves an important role in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. Fragments of endogenous damaged-associated molecular patterns, recently identified as mitochondrial DNA (mtDNA), have been proven to be a potent pro-inflammatory mediator. Epigallocatechin-3-gallate (EGCG) is able to regulate the expression levels of a series of inflammatory cytokines. However, the involvement of endogenous mtDNA in EGCG-regulated inflammatory activities in the context of myocardial I/R injury remains to be elucidated. The present study was designed to investigate the role of mtDNA in EGCG-mediated myocardial protection in a rat I/R model. Significant positive correlations between elevated plasma mtDNA copy numbers and the expression levels of tumor necrosis factor (TNF) and interleukins (IL)-6 and -8 were observed in the myocardial tissue following an I/R injury (P<0.05). However, EGCG administered prior to reperfusion was able to effectively downregulate the expression levels of plasma mtDNA, TNF and IL-6 and -8 in the myocardial tissue following an I/R injury (P<0.05). Limited infarct size, reduced severity of myocardial injury and decreased incidence of ventricular arrhythmia were observed in the EGCG-treated group. However, the beneficial effects of EGCG in preventing myocardial I/R injury may be eliminated by a specific phosphoinositide-3-kinase (PI3K) inhibitor. These results suggested that EGCG-mediated cardioprotective effects may be achieved by inhibiting the release of mtDNA from damaged mitochondria and that this protection was at least in part dependent on the PI3K/RAC-alpha serine/threonine-protein kinase associated signaling pathway.
- 出版日期2017-11
- 单位四川大学
