钠泵调节在急性呼吸窘迫综合征肺水清除中作用的研究进展  

Research advances on the role of Na^(+)-K^(+)-ATPase regulation in pulmonary edema clearance of acute respiratory distress syndrome

作　　者：温旭鹏 万齐全[1] Wen Xupeng;Wan Qiquan(Department of Transplant Surgery,the Third Xiangya Hospital of Central South University,Changsha 410013,Hunan,China)

机构地区：[1]中南大学湘雅三医院移植中心监护室,湖南长沙410013

出　　处：《中华危重病急救医学》2021年第8期1011-1016,共6页Chinese Critical Care Medicine

基　　金：湖南省自然科学基金(2020JJ4851)。

摘　　要：急性呼吸窘迫综合征(ARDS)以肺水堆积致顽固性低氧血症为特征,病死率高,潜在机制尚不清楚,当前也无特效治疗药。肺泡内水肿液主要由钠水转运系统主动转运而重吸收,Ⅱ型肺泡上皮细胞(ATⅡ)基底侧钠泵即Na^(+)-K^(+)-ATP酶介导的Na^(+)转运是肺水清除的主要动力。Na^(+)-K^(+)-ATP酶调节通过多种途径,受诸多调节因素影响,其中长期调节机制起着重要作用,即在转录水平使Na^(+)-K^(+)-ATP酶合成增多,mRNA和蛋白表达增加。Na^(+)-K^(+)-ATP酶还可通过泛素-蛋白酶体途径(UPP)和自噬-溶酶体途径降解而影响其丰度及酶活性,其中Na^(+)-K^(+)-ATP酶α1亚基起关键作用,在钠水转运中最重要。本文针对肺水清除中Na^(+)-K^(+)-ATP酶相关通路的长期调节机制以及针对这种机制探索ARDS新疗法的可能性进行综述,以期为ARDS治疗提供新的药物作用靶点。Acute respiratory distress syndrome(ARDS)is a critical disease with high mortality,and currently there is no specific treatment.ARDS is characterized by refractory hypoxemia secondary to pulmonary edema,but the underlying mechanism is not yet fully understood.Alveolar edema fluid is mainly actively transported and reabsorbed by sodium-water transport system.The sodium pump(Na^(+)-K^(+)-ATPase-mediated Na^(+)transport)on the basal side of typeⅡalveolar epithelial cells(ATⅡ)is the main driving force for pulmonary edema clearance.Na^(+)-K^(+)-ATPase regulation is affected by many regulatory factors through a variety of ways,among which"long-term regulation"mechanism plays an important role,including positively regulating the gene transcription and protein expression of Na^(+)-K^(+)-ATPase.Na^(+)-K^(+)-ATPase can also be degraded by ubiquitin-proteasome pathway(UPP)and autophagy lysosome pathway to affect its abundance and enzyme activity,meanwhile,Na^(+)-K^(+)-ATPaseα1 plays a key role in sodium water transport.We review the"long-term regulation"mechanism of Na^(+)-K^(+)-ATPase related pathways in pulmonary edema clearance and explore the possibility of new therapies for ARDS based on this mechanism,so as to provide new targets for the treatment of ARDS.

关 键 词：急性呼吸窘迫综合征 Na^(+)-K^(+)-ATP酶 肺水清除 长期调节 通路 

分 类 号：R563.8[医药卫生—呼吸系统]