摘要
肺气血屏障功能缺陷在急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)病理生理改变过程中居于中心地位,而肌球蛋白轻链激酶(MLCK)通过磷酸化肌球蛋白轻链(MLC)对其有调节作用。MLCK主要分为平滑肌型MLCK(smMLCK)、内皮型MLCK(eMLCK)和激酶相关蛋白(KRP)。它们由同一基因编码。eMLCK在ALI/ARDS中尤为重要。eMLCK有4个亚型:eMLCK2,eMLCK3a,eMLCK3b和eMLCK4,其中eMLCK2是优势亚型。脂多糖(LPS)、血小板活化因子(PAF)、凝血酶、缺血再灌注(I/R)、非正常机械应激都可以诱发ALI/ARDS,MLCK在其中发挥了重要作用。机制是MLCK使MLC磷酸化,导致细胞连接破坏,细胞骨架重排,内皮细胞收缩,并最终增加肺上皮细胞和肺内皮细胞的通透性。鉴于MLCK在ALI/ARDS中的重要性,它必将成为一个潜在的治疗靶点,在ALI/ARDS新药的研发和防治中发挥重要作用。
Air-blood barrier dysfunction is a central event in the pathophysiology of the acute lung injury（ALI）/acute respiratory distress syndrome（ARDS） and myosin light chain kinase（MLCK） regulates it by phosphorylation of myosin light chain（MLC）.MLCK is divided into smooth muscle MLCK （smMLCK）,endothelial form of MLCK（eMLCK） and kinase-related protein（KRP）.They are encoded by a single-copy gene.eMLCK is especially important in ALI/ARDS,and has 4 isoforms i.e.eMLCK2,eMLCK3a,eMLCK3b and eMLCK4.eMLCK2 is the predominant isoform.Lipopolysaccharide（LPS）,platelet activating factor（PAF）,thrombin,ischemia and reperfusion（I/R） and abnormal mechanical stress induce ALI/ARDS and MLCK plays a very important role in ALI/ARDS.The mechanisms are that MLCK phosphorylates MLC,phosphorylated MLC results in disruption of cell junctions,rearrangement of cytoskeleton,endothelial cell contraction,and at last results in hyperpermeability of epithelia and endothelia.Given the importance of MLCK in ALI/ARDS,it will become a potential drug discovery target,and play a marked role in prevention and treatment of ALI/ARDS.
出处
《军事医学科学院院刊》
CSCD
北大核心
2007年第6期572-575,578,共5页
Bulletin of the Academy of Military Medical Sciences
