CAJ | 학술논문

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 containing 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-1β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.
배경 염증소체통과계동뇌결혈후적무균성염증반응,가중대신경조직적손상,억제염증소체활화구유뇌보호작용. 목적 이NOD양수체열단백결구역상관단백3(NOD-like receptor pyrin domain containing 3,NLRP3)염증소체위핵심,통과천술염증소체재뇌결혈후적활화급기개도적중추신경계통조직손상,위상관연구영역제공삼고. 내용 NOD양수체(NOD-like receptors,NLRs)작위포내모식식별수체(pattern recognition receptors,PRRs),재뇌결혈후가식별다충위험신호,여포내저갑、삼린산선감(adenosine triphosphate,ATP)석방、산중독화활성양(reactive oxygen specises,ROS)생성등,NLRs활화형성염증소체,의차격활반광안산단백수해매(cysteinyll aspartate specific proteinase,Caspase)-1화백세포개소(interleukin,IL)-1β,개도뇌결혈후적중추신경계통(central nervous system,CNS)염증반응,가중결혈후신경조직손상.통과조공염증소체신호통로중적각개배절,포괄억제NLRs적전록、억제Caspase-1적격활혹자직접억제IL-1β,균가유효감소뇌결혈후신경조직적염증반응,발휘뇌보호작용.재체시험역증명통과길항염증소체급기하유IL-1β가명현감소결혈후뇌경사체적,제고신경공능학평분. 추향 염증소체작위뇌결혈후중추신경계통무균성염증반응적시동인자,대우뇌결혈후염증손상유중요의의.통과조공염증소체,가위림상치료뇌졸중제공신적방향.
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-1 β,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.