中文摘要
NLRP3炎症小体及其下游信号分子的激活是诱发心肌缺血后炎症反应的主要途径。通过诱导自噬,负反馈调控NLRP3炎症小体活化,进而减轻炎症反应是治疗心肌缺血再灌注损伤的关键策略。红花为菊科植物,具有活血祛瘀之功效。SY是红花的主要效应物质。临床用于冠心病等疾病的治疗,效果显著。我们前期研究发现SY及HSYA显著抑制IL-1β、IL-6升高,抑制NF-κB的表达,提示其抗炎作用是其抗MIRI的重要分子机制。进一步研究发现SY可上调线粒体自噬的相关蛋白的表达,抑制NLRP3炎症小体活化,推测其减少IL-1β分泌,减轻炎症反应可能与调控自噬,负反馈调控NLRP3活化有关。发表了4篇论文,获奖二项,本课题拟对SY主要活性成分进行构效关系研究,并探讨其对自噬及NLRP3的影响。论证其心肌保护作用可能与直接上调自噬进而抑制NLRP3的激活,抑制炎症因子表达,减少细胞凋亡有关,确证其作用信号通路与靶分子。
英文摘要
The activation of the NLRP3 inflammasome and its downstream signal pathways during myocardial ischemia/reperfusion injury (MIRI) amplify the inflammatory response and mediate further damage. Activating autophagy and inhibiting NLRP3 inflammasome may provide a pivotal strategy for prevention and treatment of MIRI. Carthamus tinctorius L., which belongs to Compositae family, has the effects of promoting blood circulation and removing blood stasis. Safflow yellow (SY), is the main bioactive ingredients of Carthamus tinctorius L., has significant effects against coronary heart disease. Our previous studies found that SY and HSYA could inhibit IL-1β、IL-6 production and decrease NF-κB expression levels, which indicates that the anti-inflammatory effects are the main mechanisms against MIRI. Further research showed that SY could up-regulate autophagy related protein expressions, diminish NLRP3 inflammasome activation, suggesting that the anti-inflammatory effects may be related tothe regulation of autophagy and then inhibition of the NLRP3 inflammasome. In this respect, 4 papers have been published and we have awarded 2 prizes. In this study, we aim to study on the structure activity relationship of the protective effects of main active safflow yellow components against the MIRI, and to investigate whether the underlying mechanisms are closely associated with the up-regulation of autophagy that leads to inhibiting NLRP3 inflammasome activation, and subsequently reducing the expression levels of inflammatory factors and cell apoptosis, thereby exploring the molecular mechanisms and targets of the cardioprotective effects of safflow yellow components.
