海水吸入型肺损伤中蛋白激酶SPAK的表达改变  

Seawater inhalation elevated the experssion of STE20/SPS1-related proline/alanine-rich kinase in seawater inhalation induced acute lung injury

作　　者：李聪聪 薄丽艳 李艳燕 陈妍 Li Congcong;Bo Liyan;Li Yanyan;Chen Yan(Department of Respiratory and Critical Care Medicine, General Hospital of Northern Theater Command, Shenyang, 110016, China;Department of Respiratory and Critical Care Medicine, Chest Hospital of Xi′an, 710038, China;Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Air Force Medical University, Xi′an, 710038, China)

机构地区：[1]中国人民解放军北部战区总医院呼吸与危重症医学科,沈阳110016 [2]陕西省西安市胸科医院呼吸与危重症医学科,西安710038 [3]空军(第四)军医大学第二附属医院呼吸与危重症医学科,西安710038

出　　处：《中华肺部疾病杂志（电子版）》2021年第2期152-157,共6页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：国家自然科学基金青年项目(81900083&81800076);中国博士后科学基金第65批面上资助(2019M653911)。

摘　　要：目的通过复制海水吸入引起的大鼠急性肺损伤模型,观察海水刺激对肺部炎症因子分泌、肺组织病理改变及肺组织中SPAK表达的影响。方法将健康雄性SD大鼠分为正常组,海水处理1 h组,海水处理3 h组,海水处理6 h组,海水处理12 h组。经气管滴注无菌海水复制海水吸入性肺损伤模型,并按照预设时间收集组织标本并检测肺组织湿干比、病理、炎性因子TNF-α、IL-1β以及SPAK的转录、翻译改变。结果海水吸入可以即刻引起血氧分压下降和二氧化碳分压升高,病理结果显示肺泡结构遭到破坏,肺泡壁断裂、增厚,中性粒细胞浸润,红细胞漏出等。ELISA结果显示海水刺激可引起肺内细胞分泌炎症因子TNF-α、IL-1β。海水吸入后SPAK蛋白表达明显增加,最高可达2.7倍左右(P<0.01),然后随着肺损伤病情的恢复,SPAK表达量逐渐下降。免疫组化染色结果显示海水吸入后SPAK表达明显升高,且广泛分布于细胞浆及细胞核。结论在高渗透压海水的刺激下肺组织细胞可以通过转录和翻译使SPAK表达增多,进而参与肺损伤时的炎症反应,加重了肺损伤程度。Objective To observe the effect of seawater stimulation on the secretion of inflammatory factors and the expression of STE20/SPS1-related proline/alanine-rich kinase(SPAK)in lung tissue of rats with seawater inhalation induced acute lung injury.Methods Sprague-Dawley(SD)rats were randomly divided into 5 groups:control group,1 h,3 h,6 h and 12 h seawater challenged groups(n=5).After challenged by endotracheal instillation of seawater to establish lung injury models,the lung tissues samples were collected and the changes of lung tissue wet dry ratio,pathology,inflammatory factors TNF-α,IL-1βand SPAK transcription and translation were detected according to the plan.Results Inhalation of seawater could immediately cause a drop of blood oxygen pressure and an increase of carbon dioxide pressure.The pathological results showed that the alveolar structure was destroyed,the alveolar wall was broken and became thicken,and neutrophil infiltration,red blood cell leakage occurred.ELISA tests showed that seawater could induce the secretion of TNF-αand IL-1β.We also detect the expression of SPAK,and the results showed that the expression of SPAK increased significantly,up to 2.7 times(P<0.01),and then decreased gradually with the recovery of lung injury.Immunohistochemical staining showed that the elevated expression of SPAK was widely distributed in the cytoplasm and nucleus.Conclusion Challenged by the hypertonic stimulation of sea water,lung cells could increase the expression of SPAK through transcription and translation,and then participate in the modulating inflammatory response,which aggravates the degree of lung injury.

关 键 词：急性呼吸窘迫综合征 海水 蛋白激酶SPAK 

分 类 号：R563[医药卫生—呼吸系统]