β2AR激动剂沙丁氨醇对脂多糖诱导的急性肺损伤肺部炎症的影响及分子机制  

Effect ofβ2AR agonist salbutamol on lung inflammation in LPS-induced acute lung injury and its molecular mechanism

作　　者：张永红[1] 李凤娟[1] 刘昀[1] 张德信[1] 李维[1] 吴媛媛[1] 柯蕊 孙秀珍[1] ZHANG Yonghong;LI Fengjuan;LIU Yun;ZHANG Dexin;LI Wei;WU Yuanyuan;KE Rui;SUN Xiuzhen(Department of Respiratory and Critical Care Medicine,Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China)

机构地区：[1]西安交通大学第二附属医院呼吸与危重症医学科,西安710004

出　　处：《山西医科大学学报》2020年第12期1345-1350,共6页Journal of Shanxi Medical University

基　　金：陕西省自然科学基金资助项目(2018JM7078)。

摘　　要：目的探讨β2肾上腺素受体(β2AR)激动剂沙丁氨醇在脂多糖(lipopolysacchride,LPS)诱导的急性肺损伤肺部炎症反应的作用及其分子机制。方法36只6-8周龄雄性BALB/c小鼠被随机分为3组:对照组(Con组)12只,无菌PBS持续雾化30 min;LPS组12只,2.5 mg/ml LPS溶液持续雾化30 min;沙丁氨醇处理组(LPS+SALB组)12只,一次性腹腔注射5 mg/kg的沙丁氨醇,间隔30 min,再给予2.5 mg/ml LPS溶液持续雾化30 min。雾化结束后第24小时处死小鼠,收集各组小鼠右肺支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),计数细胞总数及中性粒细胞分类,检测上清液TNF-α、IL-1β、IL-6浓度;取各组小鼠左肺下叶肺组织HE染色,免疫印迹方法检测左肺上叶肺组织中tristetraprolin(TTP)蛋白水平。结果LPS组小鼠BALF中细胞总数、中性粒细胞分类计数及TNF-α、IL-1β、IL-6水平均较对照组明显升高(P<0.05);LPS组肺组织的正常形态结构消失,内皮细胞和上皮细胞破坏严重,肺水肿、肺出血,以中性粒细胞为主的炎症细胞大量浸润,肺组织中TTP蛋白水平较对照组亦明显升高(P<0.05)。LPS+SALB组小鼠BALF中细胞总数、中性粒细胞分类计数以及TNF-α、IL-1β、IL-6水平较LPS组显著下降(P<0.05),肺部炎症反应较LPS组明显减轻;伴随肺组织中的TTP蛋白较LPS组明显升高(P<0.05)。结论β2AR激动剂沙丁氨醇可能通过促进TTP蛋白表达,抑制炎症因子TNF-α、IL-1β、IL-6的表达,从而抑制LPS诱导的肺部炎症损伤。Objective To investigate the effect ofβ2 adrenergic receptor(β2AR)agonist salbutamol on the inflammatory response of LPS-induced acute lung injury and its molecular mechanism.Methods Thirty-six male BALB/c mice aged 6-8 weeks were randomly divided into three groups:control group(n=12),LPS group(n=12),and salbutamol treatment group(LPS+SALB group,n=12).The mice were exposed to an aerosol of sterilized PBS alone for 30 min in control group.The mice were exposed to an aerosol of PBS containing LPS(2.5 mg/ml)for 30 min in LPS group.The mice were intraperitoneally injected with 5 mg/kg salbutamol 30 min before receiving the aerosolized LPS in LPS+SALB group.The mice were sacrificed 24 h after the end of nebulization,and then the right lung bronchoalveolar lavage fluid(BALF)was collected to count the numbers of total cell and neutrophil and detect the levels of TNF-α,IL-1β,IL-6 by ELISA.The lung tissues in lower lobe of the left lung were stained with HE,and the protein level of tristetraprolin(TTP)in the upper lobe of the left lung was detected by Western blot.Results The total number of cells,the neutrophil count and the levels of TNF-α,IL-1βand IL-6 in BALF in LPS group were significantly higher than those in control group(P<0.05).HE staining of lung tissues showed that the endothelial cells and the epithelial cells were severely damaged in model group,pulmonary edema pulmonary hemorrhage,and neutrophil-based inflammatory cells in the lung tissue were found,and the level of TTP protein in the lung tissue in LPS model group was significantly higher than that in control group(P<0.05).Compared with LPS group,the total cells,the neutrophil count and the levels of TNF-α,IL-1β,and IL-6 in BALF were decreased in LPS+SALB group(P<0.05),the LPS-induced lung histopathological changes were significantly attenuated,and the level of TTP protein in the lung tissue was significantly increased(P<0.05).Conclusion Theβ2AR agonist salbutamol may inhibit the expression of inflammatory factors TNF-α,IL-1βand IL-6 by promoting

关 键 词：急性肺损伤 急性呼吸窘迫综合征 沙丁胺醇 tristetraprolin蛋白 

分 类 号：R563[医药卫生—呼吸系统]