烟曲霉对肺微血管内皮细胞通透性的影响及可能机制

目的 探讨烟曲霉对肺微血管内皮细胞通透性的影响及其机制。方法 利用激光共聚焦扫描显微镜检测人肺微血管内皮细胞肌动蛋白（F-actin）和细胞跨膜电阻仪测定细胞跨膜电位，以观察细胞通透性的改变，并利用p38 MAPK抑制剂、ROCK抑制剂和蛋白激酶C抑制剂探讨其机制。结果 烟曲霉处理后肺微血管内皮细胞F-actin染色的荧光强度显著下降（P<0.01），烟曲霉处理组也出现细胞跨膜电阻值的显著下降（P<0.01）。与单独烟曲霉处理组比较，SB203580（20μmol/L, p38 MAPK抑制剂）干预组、Y27632（20μmol/L, ROCK抑制剂）干预组以及LY317615（10μmol/L,蛋白激酶C抑制剂）干预组的跨膜电阻值均显著上升（P<0.05）。结论 烟曲霉处理致肺微血管内皮细胞通透性增加，其机制可能涉及p38 MAPK、ROCK激酶以及蛋白激酶C通路。
Objective To investigate the effect of Aspergillus fumigatus (AF)on human pulmonary microvascular endothelial cell (HPMVEC) permeability and the related mechanisms.Methods HPMVECs were treated with AF, cell F-actin was observed with confocal laser scanning microscopy and cell transmembrane resistance was measured. In addition, the cell permeability changes in AF-treated HPMVECs were also examined with intervention of p38MAPK inhibitor SB203580 (20μmol/L), ROCK inhibitor Y27632 (20μmol/L), or PKC inhibitor LY317615 (10μmol/L), respectively. Results AF treatment induced a significant reduction of F-actin fluorescence intensity (P<0.01) and a significant reduction of cell transmembrane resistance (P<0.01) in HPMVECs. Furthermore, treatment with SB203580, Y27632 or LY317615 significantly inhibited (P<0.05) AF-induced increase of cell transmbrane resistance in HPMVECs. Conclusion AF can increase cell permeability in HMVECs, in which the MAPK (p38), ROCK and PKC pathways may be involved