中性粒细胞“异质性”在缺血性卒中的病理生理作用

PathophysiologicalRoles of Neutrophil"Heterogeneity"in Ischemic Stroke

缺血性卒中发生后,中性粒细胞会第一时间做出反应参与血脑屏障破坏、脑水肿及出血转化等病理过程,因此抗中性粒细胞治疗,如抑制其激活、粘附以及抑制蛋白酶、细胞因子释放等都曾是缺血性卒中治疗的靶点和热点。基础研究虽然前景良好,但是在向临床应用转化时却困难重重。其中一个很重要的原因就是循环血中中性粒细胞自身的“异质性”(heterogeneity)特征,即其功能和作用机制都是动态变化的。深入研究并充分了解中性粒细胞“异质性”不仅可以让我们进一步理解缺血性卒中发生后中性粒细胞发挥的病理生理作用,还可以为解决缺血性卒中基础研究向临床应用转化的瓶颈难题提供理论依据,为缺血性卒中治疗另辟蹊径。目前研究表明,在缺血性卒中病程进展过程中,中性粒细胞在发育阶段、功能、表型蛋白、患者年龄和分布等方面都存在异质性,本综述拟从以上各方面进行详细阐述。

Following ischemic stroke,neutrophils will respond immediately and participate in pathological process such as the blood-brain barrier damage,cerebral edema and hemorrhage transformation.Thus anti-neutrophils treatment such as inhibiting the activation,adhesion and the release of proteases and cytokine used to be the therapeutic target and research hotspot in ischemic stroke.Although basic research is promising,it is difficult to translate into clinical application.One important reason is the“heterogeneity”of neutrophils,e.g.their function and underlying mechanisms are dynamic.In-depth study and fully understanding the neutrophils“heterogeneity”can not only make us further understand the pathophysiological roles that neutrophils play following ischemic stroke,but also help solve the problems in the transition from basic research to clinical practice,which would pave a way for treatment of ischemic stroke.Current studies have shown that neutrophils heterogeneity exists in various aspects including developmental stage,function,the expression of phenotypic protein,patients-age relevant and distribution during the progression of ischemic stroke.This review intends to elaborate on the above aspects.