Department of Clinical Medicine of Shandong University, Jinan, Shandong 250012, China.
Chin Med J (Engl). 2013;126(15):2918-22.
p120 catenin (p120ctn) is an adheren junction protein that regulates barrier function, but its role has not been explored in alveolar edema induced by ventilation. We measured stretch-induced cell gap formation in MLE 12 cells due to the loss of p120. We hypothesized that alveolar permeability was increased by high lung inflation associated with alveolar epithelia cell tight junctions being destroyed, which resulted from the loss of p120.
Cultured MLE12 cells were subjected to being stretched or un-stretched (control) and some cells were pretreated with pp2 (c-src inhibitor). After the end of stretching for 0, 1, 2, and 4 hours, the cells were lysed, and p120 expression and c-src activation was determined by Western blotting analysis. In vivo, SD rats were taken to different tidal volumes (Vt 7 ml/kg or 40 ml/kg, PEEP = 0, respiratory rate 30-40 betas/min) for 0, 1, 2, and 4 hour and some were pretreated with pp2, and alveolar edema was calculated.
It was found that p120 expression was reduced and c-src activation increased in a time-dependent and strain-dependent manner due to cyclic-stretch of the alveolar epithelial cells. These changes could be reversed by inhibition of c-src. We obtained similar changes in rats when they were subjected to large tidal volumes and the alveolar edema increased more than in rats in the low Vt group. Pretreated the rats with inhibition of c-src had less pulmonary edema induced by the high tidal volume ventilation.
Cyclic stretch MLE 12 cells induced the loss of p120 and may be the same reason by high tidal volume ventilation in rats can aggravate alveolar edema. Maintenance of p120 expression may be a novel therapeutic strategy for the prevention and treatment of ventilation induced lung injury (VILI).
p120 连环蛋白（p120ctn）是一种黏着连接蛋白，可调节屏障功能，但在通气引起的肺泡水肿中其作用尚未得到探索。我们测量了 MLE 12 细胞因 p120 丧失而引起的拉伸诱导的细胞间隙形成。我们假设高肺充气会增加肺泡通透性，肺泡上皮细胞紧密连接被破坏，这是由于 p120 的丧失所致。
对培养的 MLE12 细胞进行拉伸或不拉伸（对照），并对一些细胞进行 pp2（c-src 抑制剂）预处理。拉伸结束后 0、1、2 和 4 小时，裂解细胞，通过 Western blot 分析测定 p120 表达和 c-src 激活。在体内，将 SD 大鼠置于不同潮气量（7 ml/kg 或 40 ml/kg，PEEP = 0，呼吸频率 30-40 次/分钟）0、1、2 和 4 小时，一些进行 pp2 预处理，并计算肺泡水肿。
发现肺泡上皮细胞周期性拉伸时，p120 表达减少，c-src 激活增加，呈时间依赖性和应变依赖性。c-src 的抑制可逆转这些变化。当大鼠接受大潮气量时，我们在大鼠中获得了类似的变化，肺泡水肿增加超过了低 Vt 组大鼠。用 c-src 抑制剂预处理大鼠，大潮气量通气引起的肺水肿减少。
周期性拉伸 MLE 12 细胞诱导 p120 丧失，高潮气量通气可能也是大鼠肺泡水肿加重的原因。维持 p120 表达可能是预防和治疗通气引起的肺损伤（VILI）的一种新的治疗策略。
