NLRP3炎性小体在动脉粥样硬化发生发展中的作用

NLRP3 inflammasome role in the occurrence and development of atherosclerosis

NLRP3炎性小体是一种包含胞内受体(主要是NOD样受体)、半胱天冬氨酸前体和凋亡相关斑点样蛋白的蛋白质复合体。该复合体最初只是被描述为一种影响感染和炎症过程的复合体,它的活化引起半胱天冬氨酶-1的激活并剪切加工底物白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-18(interleukin-18,IL-18),从而引起炎症反应;此外,炎性小体的激活过程对有氧糖酵解(瓦伯格效应,Warburg effect)有着重要的影响,这同样可以促进炎症的发生。随后的证据表明炎性小体的活化还影响很多代谢紊乱包括动脉粥样硬化(atherosclerosis,AS)、2型糖尿病、痛风和肥胖等。本综述将探讨AS与炎症、NLRP3炎性小体活化的关联性,以及瓦伯格效应如何关联炎症反应及炎性小体的激活。

The NLRP3 inflammasome is a protein complex that includes an intracellular sensor （mainly a NOD-like receptor）, the precursor procaspase-1 and the adaptor ASC. Initially the inflammasome was described as a complex which influences infection and inflammation. Inflammasome activation leads to the maturation of caspase-1 and the process of its substrates, interleukin-1β （IL-1β） and interleukin-18 （IL-18）, which leads to inflammatory response. Moreover, another feature of inflammation is that the process of activating inflammasome has a significant effect on aerobic glycolysis （＂Warburg effect＂）. Subsequent evidences have suggested that inflammasome activation affects many metabolic disorders, including atherosclerosis （AS）, type 2 diabetes, gout and obesity. We will discuss the relationship among AS, inflammation and NLRP3 inflammasome activation, and how the Warburg effect may link to inflammation and inflammasome activation in this review.