炎症小体介导脑缺血损伤的进展

State of the art of the studies on inflammasomes induced cerebral ischemic injury

背景炎症小体通过启动脑缺血后的无菌性炎症反应，加重对神经组织的损伤，抑制炎症小体活化具有脑保护作用。目的以NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor pyrin domain contmning 3，NLRP3）炎症小体为核心，通过阐述炎症小体在脑缺血后的活化及其介导的中枢神经系统组织损伤，为相关研究领域提供参考。内容NOD样受体（NOD-like receptors，NLRs）作为胞内模式识别受体（pattern recognition receptors，PRRs），在脑缺血后可识别多种危险信号，如胞内低钾、三磷酸腺苷（adenosine triphosphate，ATP）释放、酸中毒和活性氧（reactive oxygen specises，ROS）生成等，NLRs活化形成炎症小体，依次激活半胱氨酸蛋白水解酶（cysteinyll aspartate specific proteinase，Caspase）-1和白细胞介素（interleukin，IL）-1β，介导脑缺血后的中枢神经系统（central nervous system，CNS）炎症反应，加重缺血后神经组织损伤。通过调控炎症小体信号通路中的各个环节，包括抑制NLRs的转录、抑制Caspase-1的激活或者直接抑制IL-1β，均可有效减少脑缺血后神经组织的炎症反应，发挥脑保护作用。在体试验亦证明通过拮抗炎症小体及其下游IL-1岱可明显减少缺血后脑梗死体积，提高神经功能学评分。趋向炎症小体作为脑缺血后中枢神经系统无菌性炎症反应的始动因子，对于脑缺血后炎症损伤有重要意义。通过调控炎症小体，可为临床治疗脑卒中提供新的方向。

Background Inflammasome initiate the innate immune system to induce sterile inflammatory response following cerebral ischemia and exacerbate the damage of neural tissue. Targeting inflammasome signaling is supposed to inhibit inflammatory response, attenuate neurological deficits and provide neuroprotective effect after stroke. Objective In order to explore detailed information, the authors reviewed the effects and mechanisms of NOD-like receptors （NLRs） pyrin domain containing 3 （NLRP3） inflammasome after cerebral ischemia, which is the most extensively studied inflammasomes. Content NLRs, the intracellular pattern recognition receptors, can detect cellular damage and ＂intracellcular danger signals＂ following stroke, including the decrease of cytosolic K^＋ levels, extracellular adenosine triphosphate （ATP） release, acidosis, reactive oxygen specises （ROS） elevation etc. The activation and subsequent oligomerization of the NLRs form the multi-protein complexes known as inflammasomes, activating cysteinyll aspartate specific proteinase （Caspase）-1 and interleukin （IL）-1β, which in turn mediate the inflammatory response in central nervous system （CNS） and exacerbate the damage of neural tissue and neurological impairment. In addition, the activation of Caspase-1 or IL-1β, is expected to inhibit the inflammatory response and offer substantial neuroprotection. Vivo experiments also suggested that intracerebroventricular injection of IL-1β neutralizing polyclonal antibody decreased infarct volume and neurological deficits after stroke. Trend Inflammasomes mediate the initiation of CNS sterile inflammatory after cerebral ischemia, targeting inflammasome signaling may develop new therapeutics for ischemic stroke.