蛋白激酶在微血管通透性中的作用

The role of protein kinases in microvascular permeability

微血管内皮细胞层是一层半选择通透性屏障,可以调节血液中的液体、溶质和血浆蛋白进入组织间隙。在炎症刺激作用下,可通过旁细胞途径和跨细胞途径引起内皮通透性上升。旁细胞通路主要由内皮细胞间的紧密连接、黏附连接和细胞与外基质的黏着斑组成。炎症介质,如脂多糖和肿瘤坏死因子α可激活多种蛋白激酶。活化的蛋白激酶主要包括Rho相关的卷曲蛋白激酶、肌球蛋白轻链激酶、蛋白激酶C、酪氨酸激酶和丝裂原活化蛋白激酶等,参与引发内皮屏障生化和结构改变,旁细胞通路开放,导致通透性上升。该文对上述蛋白激酶在微血管通透性中作用机制的研究进展进行综述。

The microvascular endothelial cell monolayer is a semi-permeable barrier that regulates the flux of liquid, solutes and plasma proteins between the blood and interstitial space. The permeability of the endothelial cell monolayer can increase in response to inflammatory stimuli via paracellular and transcellular pathways. The paracellular pathway is predominantly composed of tight junctions, adherens junctions and focal adhesion between endothelial cells or between endothelial cell and extracellular matrix. Inflammatory mediators, such as lipopolysaccharides and tumor necrosis factor-α act on endothelial cells to activate a series of protein kinases, such as Rho-associated coiled-coil protein kinase, myosin light chain kinase, protein kinase C, protein tyrosine kinase, and mitogen activated protein kinase, which trigger biochemical and conformational changes in the barrier structure, lead to an opening of the paracellular pathway, and ultimately increase endothelial permeability. This review focuses on the regulation of the paracellular pathway and provides an overview of the mechanisms that protein kinases regulate paracellular permeability in inflammation.