尿毒症毒素对甲酚硫酸盐通过激活NLRP3炎症小体促进心肌缺血再灌注损伤的作用及机制研究

慢性肾病患者的心血管疾病发病率及病死率均高于普通人群，其中心肌缺血再灌注损伤在慢性肾病患者中受到越来越多的关注。大量的研究表明尿毒症毒素对甲酚硫酸盐（PCS）是多种心血管疾病的新型独立危险因素。然而PCS对慢性肾病患者心肌缺血再灌注损伤的致病作用尚不明确。我们的前期研究发现PCS的干预可促进小鼠心肌缺血再灌注损伤的进展。进一步机制研究表明PCS可促进小鼠心肌IL-1β的释放和心肌微血管内皮细胞中NLRP3的表达。已知NLRP3炎症小体是心肌缺血再灌注损伤的关键因子，通过分泌大量IL-1β，IL-18加重心肌损伤。因此我们推测PCS可通过激活NLRP3炎症小体促进心肌缺血再灌注损伤。我们将从细胞和动物水平揭示PCS促心肌缺血再灌注损伤的作用，并进一步探讨NLRP3炎症小体在其中的作用，以期为慢性肾病患者心肌缺血再灌注损伤的治疗提供潜在靶点。

Patients with chronic kidney disease (CKD) have higher morbidity and mortality of cardiovascular disease (CVD) compared with the general population. Among the cardiovascular diseases, myocardial ischemia/reperfusion (I/R) injury in CKD patients is getting more and more attention. Mounting studies have evidenced that a uremic toxin, p-cresol sulfate (PCS) is a novel cardiovascular risk factor in CKD patients. However, the direct effect of PCS on myocardial I/R injury is still unclear. Our previous studies have found that PCS could significantly promote myocardial I/R injury in mice. Further mechanism studies revealed that PCS could promote the expression of IL-1βand NLRP3 inflammasome in cardiac microvascular endothelial cells(CMECs). It has been demonstrated that NLRP3 inflammasome is the key point in the progression of myocardium I/R injury. So we speculate that PCS might promote myocardium I/R injury through the activity of NLRP3 inflammasome. In this study, we aimed to explore the effects of PCS on NLRP3 inflammasome, and further reveal the mechanisms of PCS promoting myocardium I/R injury, so as to find a potential target of treating I/R injury in CKD patients.