以a7nAChR为靶点治疗急性呼吸窘迫综合征及相关机制  

Treatment of acute respiratory distress syndrome by targeting a7nAChR and its related mechanism

作　　者：李孟秦[1] 王飞[2] 杨秋燕[1] 黄丹[1] 曹小平[1] LI Meng-qin;WANG Fei;YANG Qiu-yan;HUANG Dan;CAO Xiao-ping(Department of Emergency,Affiliated Hospital of North Sichuan Medical College;Department of Orthopaedics,Fifth people's Hospital of Nanchong,Nanchong 637000,Sichuan,China)

机构地区：[1]川北医学院附属医院急诊医学科 [2]南充市第五人民医院骨科,四川南充637000

出　　处：《川北医学院学报》2022年第4期421-425,共5页Journal of North Sichuan Medical College

基　　金：四川省南充市市校科技战略合作专项资金(19SXHZ0056)。

摘　　要：目的:探讨a7胆碱能受体(a7nAChR)在急性呼吸窘迫综合征(ARDS)中的作用及兴奋a7nAChR减轻LPS诱导小鼠急性肺损伤的相关机制。方法:将20~75岁的男性ARDS患者分为吸烟组与非吸烟组,入院后24 h内检测血浆中IL-17、IL-6、TNF-α浓度。24只小鼠随机分为对照组、LPS组、LPS+a7nAChR激动剂组、LPS+a7nAChR抑制剂组,每组各6只。造模前1 h,LPS+a7nAChR激动剂、LPS+a7nAChR抑制剂组小鼠分别予以腹腔注射choline(10 mg/kg)、α-bungarotoxin(1μg/kg)。然后对照组通过气管导管滴注PBS溶液,其余3组小鼠气管导管内滴注LPS溶液建立小鼠ARDS模型。检测支气管肺泡灌洗液(BALF)中IL-17、IL-6、TNF-α水平。取左下肺组织行HE染色、肺损伤评分,右肺测肺组织湿/干比重,左上肺测RORγt蛋白及mRNA水平。结果:男性ARDS患者中,吸烟者外周血IL-17、IL-6、TNF-α水平低于非吸烟者(P<0.05)。a7nAChR激动剂降低小鼠肺损伤评分及肺组织湿/干比重(P<0.05),而a7nAChR抑制剂使其进一步升高(P<0.05)。肺损伤小鼠BALF中IL-17、IL-6、TNF-α水平较对照组升高(P<0.05),a7nAChR兴奋剂可使其降低(P<0.05),而a7nAChR抑制剂可使其进一步升高(P<0.05)。肺损伤小鼠肺组织RORγt蛋白及mRNA水平较对照组升高(P<0.05),a7nAChR兴奋剂可下调其表达(P<0.05),而a7nAChR抑制剂可使其表达进一步上调(P<0.05)。结论:抑制a7nAChR可能通过在转录及翻译水平抑制RORγt表达减轻Th17细胞反应性反应,从而抑制炎症反应,减轻肺损伤。Objective:To investigate the role of a7nAChR in acute respiratory disease syndrome(ARDS)and the mechanism of a7nAChR agonists alleviating LPS-induced acute lung injury in mice.Methods:Male ARDS patients aged 20-75 years were divided into smoking group and non-smoking group.The concentrations of IL-17,IL-6 and TNF-α in plasma were measured by ELISA within 24 hours after admission.24 mice were randomly divided into 4 groups:control group,LPS group,LPS+a7nAChR agonists group,LPS+a7nAChR inhibitor group,6 mice in each group.1 hour before modeling,mice in LPS+a7nAChR agonists and LPS+a7nAChR inhibitor groups were intraperitoneally injected choline(10mg/kg)andα-Bungarotoxin(1μg/kg),respectively.The control group was given PBS solution through tracheal tube,and the other three groups were given LPS solution to establish mouse ARDS model.The mice were sacrificed 48 h later,and bronchoalveolar lavage fluid(BALF)was collected to detect the levels of IL-17,IL-6 and TNF-α.The lower left lung tissue was stained with HE and scored for lung injury.The wet/dry proportion of lung tissue was measured in the right lung,and the protein and mRNA levels of RORγT were measured in the upper left lung.Results:In enrolled ARDS patients,the levels of IL-17,IL-6 and TNF-αin plasma of smokers were significantly lower than those of non-smokers(P<0.05).a7nAChR agonists decreased lung injury score and wet/dry ratio of lung tissue in ARDS/ALI mice,while a7nAChR inhibitor further increased lung injury score and wet/dry proportion of lung tissue in the ARDS/ALI mice(P<0.05).Compared with the control group,the levels of IL-17,IL-6 and TNF-α in BALF of ARDS/ALI mice were significantly increased,which were decreased by a7nAChR agonists while were further increased by a7nAChR inhibitor(P<0.05).The protein and mRNA of RORγt expression in lung tissue of ARDS/ALI mice were significantly upregulated when compared with control group,which was downregulated by a7nAChR agonists while further upregulated by while a7nAChR inhibitor(P<0.05).Conclusion:I

关 键 词：急性呼吸窘迫综合征 急性肺损伤 a7胆碱能受体 白细胞介素-17 炎症反应 

分 类 号：R563.9[医药卫生—呼吸系统]