基于NF-κB和NLRP3炎症小体通路激活炎症反应角度研究甘蔗叶多糖防治糖尿病心肌病的分子机制

糖尿病心肌病(DCM)是糖尿病的主要并发症，急需开发安全有效的药物。心肌炎症反应是DCM心肌损伤的重要发病机制，而NLRP3和NF-κB 信号通路是DCM炎症过程中的两条重要通路。项目组在国家自然科学基金项目的资助下，发现甘蔗叶多糖(SLP)能改善糖尿病小鼠的心肌炎症损伤，保护心肌功能，但其分子机制尚不清楚。项目组前期研究还表明，SLP具有抗氧化作用，并对NF-κB 和NLRP3信号通路的相关炎症因子TNF-α、IL-1β、IL-2、IL-17具有调控作用。因此，基于以上实验证据及DCM病理过程，提出科学假说：SLP有可能通过影响NF-κB信号通路、NLRP3炎症小体活化及其相互作用所激活的炎症反应，进而起到抑制糖尿病性心肌损害的作用。本项目将围绕以上假说，通过体内外实验，观察SLP对NF-κB 和NLRP3信号通路多个环节及二者相互影响的调控作用，阐明其防治DCM的分子机制。

Diabetic cardiomyopathy (DCM) is a major complication of diabetes. Myocardial inflammatory injury is an important pathogenesis of DCM, and NLRP3 and NF-κB signaling pathways are two important pathways in the inflammatory process of DCM. Funded by the national natural science foundation of China, the research group found that sugarcane leaf polysaccharide (SLP) can improve myocardial inflammatory injury and protect myocardial function in diabetic mice, but the molecular mechanism is still unclear. Preliminary studies of the project team showed that SLP exhibited antioxidant effects and showed regulatory effects on the related factors of NF-κB and NLRP3 signaling pathways, such as TNF-α, IL-1β, IL-2 and IL-17.Therefore, based on the above experimental evidence and the pathological process of DCM, the following scientific hypothesis was proposed :SLP may play a role in inhibiting myocardial injury in DCM by affecting the inflammatory response activated by NF-κB signaling pathway, NLRP3 inflammasome activation and their interactions. This project will focus on the above hypothesis, observe the regulatory effects of SLP on NF-κB and NLRP3 signaling pathways and their interactions via in vitro and in vivo experiments, and elucidate the molecular mechanism of SLP in the prevention and treatment of DCM.