七氟醚下调TRPV4/C-PLA2信号通路活性减轻呼吸机诱导的大鼠肺损伤  

Sevoflurane alleviates ventilator-induced lung injury in rats by down-regulating the TRPV4/C-PLA2 signaling pathway

作　　者：王文法 杨泳[2] 王莉[3] 郭欣[3] 田玲芳 王鹤 胡玉珍 刘睿[3] WANG Wenfa;YANG Yong;WANG LI;GUO Xin;TIAN Lingfang;WANG He;HU Yuzhen;LIU Rui(Department of Anesthesiology,Chuxiong Yi Autonomous Prefecture People's Hospital,Chuxiong 675000,China;Experimental Center of Medical Function,Kunming Medical University,Kunming 650500,China;Department of Anesthesiology,First People's Hospital of Yunnan Province/Affiliated Hospital of Kunming University of Science and Technology,Kunming 650032,China)

机构地区：[1]楚雄彝族自治州人民医院麻醉科,云南楚雄675000 [2]昆明医科大学医学机能实验中心,云南昆明650500 [3]云南省第一人民医院//昆明理工大学附属医院麻醉科,云南昆明650032

出　　处：《南方医科大学学报》2023年第11期1886-1891,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(81760018);云南省科技厅地方高校联合专项(202001BA070001-146);云南省第一人民医院临床医学中心开放项目(2022YJZX-FC22)。

摘　　要：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。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.

关 键 词：机械通气 呼吸机诱导的肺损伤 七氟醚 瞬时受体电位香草酸亚型4 胞质型磷脂酶A2 

分 类 号：R614[医药卫生—麻醉学]