转录因子GABPA对机械通气相关肺损伤中调控紧密连接蛋白的影响

Effect of GABPA on the Regulation of Tight Junction in Ventilation-Induced Lung Injury

摘要: 目的：探讨转录因子GABPA在机械通气相关肺损伤中对紧密连接蛋白Occludin表达的影响。方法：对小鼠肺上皮细胞(MLE-12)进行机械牵张，牵张时间为0 h、2 h、4 h，牵张幅度为20%。利用GABPA siRNA预处理MLE-12敲低GABPA基因48 h后，再对MLE-12细胞进行机械牵张，牵张时间为0 h、4 h，牵张幅度为20%。机械牵张后，提取蛋白后，利用蛋白质印迹法检测GABPA和Occludin的表达。结果：与CS (0 h)组比较，CS (2 h)组、CS (4 h)组中GABPA表达均升高(P < 0.05)、Occludin表达均降低(P < 0.05)。与CS (4 h) si-Nc组比较，CS (4 h) si-GABPA组Occludin表达升高(P < 0.05)。结论：机械牵张导致VILI中的转录因子GABPA表达升高，紧密连接蛋Occludin表达降低；GABPA在调控Occludin中起重要作用，是VILI潜在治疗靶点。

Abstract: Objective: To investigate the effect of GABPA on the expression of Occludin in ventilator-induced lung injury. Methods: MLE-12 cells were treated with cyclic stretch with 20% amplitude for 0 h, 2 h, 4 h. MLE-12 cells were pre-treated with GABPA siRNA to knock down GABPA gene for 48 h, and then treated with cyclic stretch with 20% amplitude for 0 h and 4 h. After cyclic stretch, the protein of MLE-12 cells was extracted, and the expressions of GABPA and Occludin were detected by Western blotting. Results: Compared with CS (0 h) group, the expression of GABPA increased in CS (2 h) group and CS (4 h) group (P < 0.05), and the expression of Occludin decreased (P < 0.05). Compared with CS (4 h) si-Nc group, the expression of Occludin increased in CS (4 h) si-GABPA group (P < 0.05). Conclusion: Mechanical stretch increased the expression of GABPA and decreased the expression of Occludin in VILI. GABPA plays an important role in regulating Occludin and is a potential therapeutic target in VILI.