神经型一氧化氮合酶在脓毒症中的作用研究进展

Research progress on role of neuronal oxide synthase in sepsis

脓毒症目前仍是全球公共卫生领域面临的严峻挑战,一般是微生物感染引起的全身炎症反应综合征,多由先天免疫系统参与,最终导致全身多器官功能衰竭。目前脓毒症的病死率仍较高,但并无特效治疗方案,早期发现、早期干预对脓毒症来说是十分重要的。脓毒症3.0的定义主要有两点,第一是感染,第二是器官功能障碍。而影响脓毒症进展的因素很多,如病原体类型、感染部位、干预时机、免疫系统功能的强弱等;致病机制主要是炎症,炎症相关基因在脓毒症发病过程中异常表达。一氧化氮合酶(NOS)是一种存在于内皮细胞、巨噬细胞、神经细胞等中的同工酶,可分为神经型、诱导型、内皮型3型。诱导型NOS(iNOS)和内皮型NOS(eNOS)在炎症反应中的作用明确,但神经型NOS(nNOS)在脓毒症中的作用目前尚未完全阐明。一氧化氮(NO)可以使血管扩张而起调节血压的作用,在神经转导中也有一定作用;更重要的是NO是一种炎症介质,可能会加重炎症反应,活性氮簇(RNS)本身作为一种氧化应激产物也会促进炎症的进展。本文就nNOS在脓毒症发病过程中的作用和可能机制的研究进展进行综述。

At present,sepsis is still a severe challenge to the field of global public health.It is generally a systemic inflammatory response syndrome caused by microbial infection,mostly involving the innate immune system,and ultimately leading to systemic multi-organ failure.The mortality of sepsis is still high right now,but there is no specific treatment plan,early detection and intervention was still very important for sepsis.Sepsis 3.0 is mainly defined by two points:infection and organ dysfunction.There are many factors affecting the progression of sepsis,such as pathogen type,infection site,timing of intervention,strength of immune system strong or weak,etc.;the main pathogenic mechanisms are inflammation and abnormal expressions of inflammation-related genes involved in the pathogenic processes of sepsis.nitric oxide synthase(NOS)is a kind of isoenzyme existing in endothelial cells,macrophages,nerve cells,etc,which can be divided into 3 types:neural,inducible and endothelial types.The roles of inducible NOS(iNOS)and endothelial NOS(eNOS)of inflammatory response are clear,but the role of neuronal NOS(nNOS)in sepsis has not been fully elucidated.Nitric oxide(NO)can dilate blood vessels and play a role in regulating blood pressure,and it also plays a certain role in nerve transduction;more importantly,NO is an inflammatory mediator,which may aggravate the inflammatory response,and reactive nitrogen species(RNS)themselves,as an oxidative stress product,can also promote the progress of inflammation.This article reviews the research progress of the role and possible mechanism of nNOS in the pathogenesis of sepsis.