缺血性卒中中后期炎症反应机制研究进展与新药研发的契机

Advance in mechanism study of inflammation in post-ischemic stroke and opportunity of new drug development

由DAMPs介导的炎症反应主导了缺血性脑卒中的中、后期主要损伤病理过程。在此过程中,由免疫细胞活化并产生的各种炎性细胞因子、趋化因子和其他细胞毒性介质,是触发缺血后炎症的关键因素。与此同时,这一机制也触发了抗炎和修复型免疫细胞的形成。以DAMPs-TLR-NF-κB炎症激活链为主轴的靶向抗卒中新药研究,已逐渐成为当今探索卒中新治疗手段的方向,同时也为临床治疗中抗炎管理提供了理论依据。该文总结了近期在缺血性脑损伤与脑部炎症的机制研究,并重点探讨了以巨噬细胞DAMPs-TLR-NF-κB激活链为主轴的靶向卒中治疗新药研究现状与未来的发展趋势。

Inflammation mediated by the damage-associated molecular patterns(DAMPs) moleculesdominates the pathological process of ischemic stroke in the middle and late stages.In this process,the activation of immune cells and subsequent production of various inflammatory cytokines,chemokines and other cytotoxic mediators are the key factors that trigger inflammation injuries after ischemia.Meanwhile,this mechanism also induces the formation of immune cells with anti-inflammatory activities and tissue repair properties,boosting the regeneration of damaged never system.DAMPs-TLR-NF-κB inflammatory activation chain as the main axis of new anti-stroke drug approaches has become a direction to explore the novel treatments of stroke,which also provides a rational basis for anti-inflammatory therapy in clinical practice for stroke patients.In this paper,we highlighted the current status on the mechanism study with focus on the activation chain of macrophage and microglia involved in DAMPs-TLR-NF-κB in inflammation after stroke and discussed the future development in searching the potential new treatments and therapeutic agents which could be applied in clinics.