地塞米松对急性肺损伤中TREM-1表达的影响
骆凤,郑浩翔,董良,李年旺,周琴,贾哲,贺丽萍,孙国瑛
中国临床解剖学杂志 ›› 2016, Vol. 34 ›› Issue (5) : 523-527.
地塞米松对急性肺损伤中TREM-1表达的影响
Effect of dexamethasone on the expression of TREM-1 in acute lung injury
目的 探讨地塞米松（Dexamethasone，Dex）对脂多糖（Lipopolysaccharide, LPS）诱导的急性肺损伤(acute lung injury, ALI)小鼠肺组织中髓样细胞表达的触发受体1（triggering receptor expressed on myeloid cells-1,TREM-1）表达的影响。 方法 以昆明小鼠为研究对象，腹腔注射LPS(10 mg/kg)建立ALI模型，30 min后给予不同浓度的Dex（5、10、20、40 mg/kg）处理6 h；选用Dex(10 mg/kg)处理不同的时间（6、12、24、36 h）。HE染色法观察肺组织病理损伤程度； RT-PCR检测肺组织TREM-1mRNA的表达；ELISA检测小鼠支气管肺泡灌洗液中可溶性TREM-1（sTREM-1）蛋白水平。 结果 Dex可减轻肺病理损伤；Dex呈时间依赖性地下调ALI小鼠肺组织的TREM-1 mRNA的表达，且在6 h即可降低；Dex呈剂量依赖地下调ALI小鼠肺组织中TREM-1 mRNA的表达，并在10 mg/kg时开始降低。Dex可降低ALI小鼠支气管肺泡灌洗液中sTREM-1的蛋白水平。 结论 Dex可呈剂量及时间依赖性下调ALI小鼠肺组织中的TREM-1mRNA的表达，并减少肺内髓样细胞胞膜TREM-1的脱落，提示Dex可能通过调节TREM-1的表达，从而抑制ALI早期的炎症级联反应，参与保护肺组织。
Objective To investigate the effects of dexamethasone (Dex) on the TREM-1expression in acute lung injury(ALI) of mice induced by lipopolysaccharide (LPS). Methods Kunming mice (KM mice) were used as the research object and LPS (10 mg/kg) was used to induce acute lung injury model. After half an hour given different concentrations of Dex (5, 10, 20, 40 mg/kg) and selection of different time points (6, 12, 24 and 36 h) were observed. The lung tissue was observed by HE staining, RT-PCR was used to detect TREM-1 expression, and ELISA was used to detect the expression of sTREM-1 in bronchoalveolar lavage fluid of mice. Results Dex could time-dependently down-regulate the expression of lung tissue in the acute lung injury and in 6h treatment peak; Dexcould dose-dependently down-regulate TREM-1 expression in acute lung injury of lung tissue, and reached the peak at 10 mg /kg. Dex could decrease the protein level of sTREM-1 in bronchoalveolar lavage fluid of ALI mice. Conclusion Dex can down-regulate TREM-1 of lung tissues of ALI mice in a dose and time-dependent manner, and reduce myeloid cell membrane of TREM-1 in lung. Our research indicates that Dex may inhibit inflammatory cascade and protect lung tissue by regulation of TREM-1 expression.
髓样细胞表达的触发受体-1 / 急性肺损伤 / 地塞米松 / 脂多糖
Triggering receptor expressed on myeloid cells-1 / Acute lung injury / Dexamethasone;Lipopolysaccharide
[1] 陈英华，吕嘉文，翟启良，等。LPS直接及间接作用致小鼠急性肺损伤模型的建立[J].中国临床解剖学杂志, 2015, 33(4):439-443.
[2] Panico FF, Troster EJ, Oliveira CS, et al. Risk factors for mortality and outcomes in pediatric acute lung injury/acute respiratory distress syndrome[J]. Pediatr Crit Care Med, 2015, 16(7):e194-200.
[3] 宋卓慧， 孙国瑛， 周勇. 脂多糖对小鼠巨噬细胞TREM-1表达的影响[J].长治医学院学报, 2012, 26(2) :81-83.
[4] Azoulay É, Canet E, Raffoux E. Dexamethasone in patients with acute lung injury from acute monocytic leukaemia[J]. Eur Respir J, 2012, 39(3):648-653.
[5] Sun GY, Guan CX, Zhou Y, et al. Vasoactive intestinal peptide re-balances TREM-1/TREM-2 ratio in acute lung injury[J].Regulatory Peptides, 2011, 25(1):56-64.
[6] Su Z, Liao J, Liu Y, et al. Protective effects of patchouli alcohol isolated from Pogostemon cablin on lipopolysaccharideinduced acute lung injury in mice[J]. Exp Ther Med, 2016, 11(2):674-682.
[7] Frank EA, Birch ME, Yadav JS. MyD88 mediates in vivo effector functions of alveolar macrophages in acute lung inflammatory responses to carbon nanotube exposure [J]. Toxicol Appl Pharmacol, 2015, 288(3):322-329.
[8] Han X, Wang Y, Chen H, et al. Enhancement of ICAM-1 via the JAK2/STAT3 signaling pathway in a rat model of severe acute pancreatitis-associated lung injury [J]. Ther Med, 2016, 11(3):788-796.
[9] 康连华. 地塞米松联合沐舒坦雾化吸入治疗矽肺合并肺部感染疗效观察[J].中国保健营养, 2013, 23(6):1415-1416.
[10] Bucova M, Suchankova M, Tibenska E, et al. Diagnostic value of TREM-1 and TREM-2 expression in bronchoalveolar lavage fluid in sarcoidosis and other lung diseases[J]. Bratisl Lek Listy, 2015, 116(12):707-713.
[11] Yuan Z, Syed M, Panchal D, et al. TREM-1-accentuated lung injury via miR-155 is inhibited by LP17 nanomedicine[J]. Am J Physiol Lung Cell Mol Physiol, 2016, 310(5):L426-438.
[12] Kim HA, Park JH, Lee S, et al. Combined delivery of dexamethasone and plasmid DNA in an animal model of LPS-induced acute lung injury[J]. J Control Release, 2011, 156(1):60-69.
[13] von Bismarck P, Klemm K, García Wistädt CF, et al. Selective NF-κB inhibition, but not dexamethasone, decreases acute lung injury in a newborn piglet airway inflammation model [J]. Pulm Pharmacol Ther, 2009, 22(4):297-304.
[14] Duffy BA, Chun KP, Ma D, et al. Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus[J]. Neurobiol Dis, 2014, 63:229-236.
湖南省教育厅科研项目(14C0703)；中南大学博士后基金（160320001）；2015年湖南师范大学树达学院创新课题（012-615）
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