NALP3炎性体活化对脓毒症发病过程中HMGB1释放的调节作用

The regulating effect of NALP3 inflammasome on HMGB1 release in the pathogenetic progess of sepsis

失控性全身炎性反应和免疫功能障碍是脓毒症发生的主要病理生理过程。HMGB1是脓毒症致死效应的最重要的晚期炎性递质,HMGB1由病原体或早期炎性反应分子活化免疫细胞释放,在脓毒症的发生、发展过程中它不仅发挥促炎效应,而且还与细胞免疫功能障碍密切相关。脓毒症和内毒素血症中HMGB1的分泌和释放继发于NALP3炎性体的活化。越来越多的证据表明,炎性体(尤其是NALP3炎性体)对单核/巨噬细胞释放HMGB1起着重要的调节作用。在炎性反应过程中,免疫细胞主动释放HMGB1的过程主要以一种炎性反应小体参与的、依赖caspase活化的方式进行。通过调节NALP3炎性体活化,抑制HMGB1释放,调节免疫功能紊乱状态,为脓毒症等免疫紊乱相关疾病的治疗提供了新的策略。

Uncontrolled systemic inflammatory response and immune dysfunction are the major pathophysiological process of sep- sis. High mobility group protein B1 （ HMGB1 ） is one of the most important terminal inflammatm3, mediators leading to the lethal effect of severe sepsis. HMGB1 is released by pathogens or immune cells activated by early inflammatory factors, and it not only plays a pro-inflammatory effect in the occurrence and development of sepsis,but also closely related to cellular immune dysfunc- tion. The secretion and release of HMGB1 in sepsis as well as endotoxemia are seeonda~~ to the activation of inflammasome. More and more evidences show that inflammasome（ especially NALP3 ） plays an important role regulating the release of HMGB1 for mon- oeytes/nmcrophages. In the inflamnmtion, the immune cells release HMGB1 actively. This progress require a kind of inflamma- somes,and it depends on the activation of caspase activation. It provides a new strategy for the treatment of immune disorders such as sepsis by adjusting the activation of NALP3 ,restrain the release of HMGB1 and regulating immune dysfunction.