Objective: To explore the mechanism underlying the protective effect of sevoflurane against ventilator-induced lung injury (VILI).
Methods: Thirty-two SD rats were randomized into mechanical ventilation (MV) group, MV+sevoflurane group (MS group), MV+sevoflurane+transient receptor potential vanillate subtype 4 (TRPV4) agonist group (MST group) and MV+ sevoflurane + vehicle group (MSV group). Arachidonic acid (AA) in the lung tissues was quantified with ELISA. TRPV4, cytoplasmic phospholipase A2 (C-PLA2) and myosin light chain kinase (MLCK) protein expressions were detected by Western blotting. Lung injury in the rats was evaluated by assessing MLCK protein expression level, pulmonary permeability index, lung wet/dry ratio, leukocyte count in the bronchoalveolar lavage fluid (BALF), myeloperoxidase content in lung tissue, and histological score of the lungs.
Results: The rats in MV group showed significantly increased TRPV4 and C-PLA2 expression levels in the lung tissues with increased lung permeability and obvious lung inflammation compared with those in the other 3 groups (P < 0.05). No significant differences were found in the parameters associated with lung injuries between MS group and MSV group. Compared with those in MST group, the rats in MS group and MSV group showed significantly reduced AA production and TRPV4 and C-PLA2 expressions in the lungs (P < 0.05) with alleviated lung hyper-permeability and inflammation (P < 0.05).
Conclusion: Sevoflurane protects against VILI in rats by down-regulating the TRPV4/C-PLA2 signaling pathway.
目的: 探讨七氟醚抗呼吸机诱导的肺损伤(VILI)的保护作用机制。
方法: 32只SPF级SD大鼠随机平均分为4组(8只/组)：机械通气(MV)组、MV+七氟醚组(MS组)、MV+七氟醚+瞬时受体电位香草酸亚型4(TRPV4)激动剂组(MST组)和MV+ 七氟醚+溶剂组(MSV组)。ELISA检测实验大鼠肺组织花生四烯酸(AA)含量；Western blotting检测TRPV4、胞质型磷脂酶A2 (C-PLA2)和肌球蛋白轻链激酶(MLCK)蛋白表达水平；以MLCK表达水平、肺通透性指数和肺湿/干比值反映肺通透性，支气管肺泡灌洗液(BALF)中多形核白细胞计数和肺组织髓过氧化物酶活性用于反映肺炎症反应程度，并对肺组织形态学进行评分。
结果: 与其余3组相比，MV组实验大鼠肺组织TRPV4和C-PLA2表达增高(P < 0.05)，同时伴有明显的肺通透性增加和肺炎症反应(P < 0.05)；MS组与MSV组各检测指标差异无统计学意义(P>0.05)；与MST组相比，MS组和MSV组实验大鼠AA生成明显减少(P < 0.05)，TRPV4和C-PLA2表达下调(P < 0.05)，肺通透性增加和肺炎症反应明显减轻(P < 0.05)。
结论: 七氟醚下调TRPV4/C-PLA2信号通路发挥其抗VILI保护作用。
Keywords: cytoplasmic phospholipase A2; mechanical ventilation; sevoflurane; transient receptor potential vanillate subtype 4; ventilator-induced lung injury.