Akt/NF-κB信号通路介导NSC23766预先处理对呼吸机相关性肺炎大鼠内皮功能的保护作用  

Protective Effect of NSC23766 Pretreatment Mediated via Akt/NF-κB Signaling Pathway on Endothelial Function in Rats with Ventilator-associated Pneumonia

作　　者：徐冬 余健 陈勇[1] 薛翠 宋玲英[1] 陈琳[1] 孔天翔 XU Dong;YU Jian;CHEN Lin;XUE Cui;SONG Ling-ying;KONG Tian-xiang(Department of Critical Carethe First Affiliated Hospital of Hubei Institute of Science and Technology,Xianning,Hubei 437100,China;Oncology department,the First Affiliated Hospital of Hubei Institute of Science and Technology,Xianning,Hubei 437100,China;Intensive Care Unit,People's Hospital of Tongshan County,Xianning,Hubei 437600,China)

机构地区：[1]咸宁市中心医院湖北科技学院附属第一医院重症医学科,湖北咸宁437100 [2]咸宁市中心医院湖北科技学院附属第一医院肿瘤科,湖北咸宁437100 [3]通山县人民医院重症监护室,湖北通山437600

出　　处：《解放军医药杂志》2020年第5期19-23,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：湖北省自然科学基金资助项目(2014CKB532)。

摘　　要：目的基于丝苏氨酸激酶/核转录因子-κB(Akt/NF-κB)信号通路探讨NSC23766预先处理对呼吸机相关性肺炎(VILI)大鼠内皮功能的保护作用及机制。方法选取SD大鼠36只,随机分为对照组、模型组和NSC23766组,每组12只。模型组和NSC23766组大鼠均采用大潮气量法复制VILI模型;NSC23766组大鼠在连接呼吸机前经气管导管滴入NSC23766(1.5 mg/kg)预处理1 h。机械通气4 h后,观察肺组织的病理变化;检测大鼠肺组织湿重/干重(W/D)值和支气管肺泡灌洗液(BALF)中白介素(IL)-1β、IL-10、肿瘤坏死因子(TNF)-α、总蛋白、白细胞数(WBC),肺组织中一氧化氮(NO)、内皮素-1(ET-1)、诱导型一氧化氮合酶(iNOS)和内皮型一氧化氮合酶(eNOS)mRNA水平,Akt/NF-κB信号通路的磷酸化水平。结果模型组和NSC23766组大鼠肺组织W/D值、NO、ET-1和iNOS mRNA水平均高于对照组,且NSC23766组上述指标低于模型组(P<0.05,P<0.01)。模型组和NSC23766组eNOS mRNA低于对照组,且NSC23766组高于模型组(P<0.05,P<0.01)。模型组和NSC23766组大鼠肺组织p-Akt/Akt和p-NF-κB p65/NF-κB p65表达水平高于对照组,且NSC23766组上述指标低于模型组(P<0.01)。模型组和NSC23766组大鼠BALF中总蛋白、WBC、IL-1β、IL-6和TNF-α水平高于对照组,且NSC23766组上述指标低于模型组(P<0.05,P<0.01)。结论 NSC23766可能通过抑制VILI大鼠Akt/NF-κB信号通路,降低肺组织炎性因子、NO和ET-1水平,保护肺血管内皮细胞结构和功能。Objective To explore of protective effect and mechanism of NSC23766 pretreatment on endothelial function of ventilator-associated pneumonia(VAP) rats based on serine/threonine protein kinase/nuclear transcription factor-κB(Akt/NF-κB) signaling pathway. Methods Thirty-six SD rats were randomly divided into control group, model group and NSC23766 group, with 12 cases in each group. In model group and NSC23766 group, VAP models were replicated by large tidal volume method. The rats in NSC23766 group were pretreated with NSC23766(1.5 mg/kg) for 1 h by tracheal catheter before connecting to the ventilator. At 4 h after mechanical ventilation, pathological changes of lung tissue were observed. Wet weight/dry weight(W/D) of lung tissue, levels of interleukin-1β(IL-1β), IL-10 and tumor necrosis factor α(TNF-α) in bronchoalveolar lavage fluid(BALF), total protein and white blood cell count(WBC), nitric oxide(NO), endothelin-1(ET-1), inducible nitric oxide synthase(iNOS) and endothelial nitric oxide synthase(eNOS) mRNA in lung tissue, and phosphorylation level of Akt/NF-κB signal pathway were detected. Results The levels of W/D, NO, ET-1 and iNOS mRNA in lung tissue of model group and NSC23766 group were higher than those of control group, and the levels of above indicators in NSC23766 group were lower than those of model group(P<0.05). eNOS mRNA was lower in model group and NSC23766 group than in control group, and the level was higher in NSC23766 group than in control group(P<0.05). The expression levels of p-Akt/Akt and p-nf-κB p65/NF-κ B p65 in lung tissue of model group and NSC23766 group were higher than those of control group, and the levels in NSC23766 group were higher than those of model group(P<0.01). The levels of total protein, WBC, IL-1 β, IL-6 and TNF-α in BALF of model group and NSC23766 group were significantly higher than those of control group, and the levels in NSC23766 group were lower than those of model group(P<0.05, P<0.01). Conclusion NSC23766 may reduce levels of inflammatory factors, N

关 键 词：肺炎 呼吸机相关性 NSC23766 Akt/NF-κB信号通路 白介素-1Β 肿瘤坏死因子-α 大鼠 Sprague-Dawley 

分 类 号：R-332[医药卫生] R563.1