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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。
Dysfunction in the pulmonary blood-plasma barrier is central to the pathophysiology of acute lung injury / acute respiratory distress syndrome (ALI / ARDS), whereas myosin light chain kinase (MLCK) is phosphorylated by myosin light chain (MLC ) Have a regulatory role. MLCK is mainly divided into smooth muscle MLCK (smMLCK), endothelial MLCK (eMLCK) and kinase-related protein (KRP). They are encoded by the same gene. eMLCK is especially important in ALI / ARDS. There are 4 subtypes of eMLCKs: eMLCK2, eMLCK3a, eMLCK3b and eMLCK4, of which eMLCK2 is the dominant subtype. Lipopolysaccharide (LPS), platelet activating factor (PAF), thrombin, ischemia / reperfusion (I / R), abnormal mechanical stress can induce ALI / ARDS, MLCK play an important role. The mechanism is that MLCK phosphorylates MLC, resulting in disrupted cell junctions, cytoskeletal rearrangements, endothelial cell contraction, and ultimately increased permeability of lung epithelial and pulmonary endothelial cells. Given the importance of MLCK in ALI / ARDS, it will become a potential therapeutic target and play an important role in the development and prevention of new ALI / ARDS drugs.