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脂多糖对呼吸道合胞病毒感染小鼠气道炎症及气道高反应性的影响及其机制研究

The effects of lipopolysaccharide on airway inflammation and hyper-responsiveness induced by respiratory syncytial virus infection and its mechanism

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【作者】 周娜谢晓虹邓昱臧娜李伟王莉佳刘恩梅

【Author】 ZHOU Na;XIE Xiaohong;DENG Yu;ZANG Na;LI Wei;WANG Lijia;LIU Enmei;Ministry of Education Key Laboratory of Child Development and Disorder,Key Laboratory of Pediatrics in Chongqing,Chongqing International Science and Technology Cooperation Center for Child Development and Disorders;Department of Respiratory Medicine,Children’s Hospital of Chongqing Medical University;

【机构】 儿童发育疾病研究教育部重点实验室儿科学重庆市重点实验室重庆市儿童发育重大疾病诊治与预防国际科技合作基地重庆医科大学附属儿童医院呼吸中心一病房

【摘要】 目的探讨脂多糖(LPS)对呼吸道合胞病毒(RSV)感染小鼠的气道炎症及气道高反应性的影响及其机制。方法将6~8周龄雌性Balb/c小鼠分为4组:对照组、LPS组、RSV组及RSV+LPS组,于首次处理后第7天收取肺组织、肺泡灌洗液标本,QPCR检测肺组织病毒拷贝数,计数肺泡灌洗液(BALF)中细胞总数及分类计数,H&E染色观察肺部病理损伤,肺功能测定AHR,Western blot检测TRIF和MyD88蛋白表达,ELISA检测BALF中IFN-γ、KC、IL-1β、IL-6质量浓度。结果 RSV+LPS组病毒拷贝数与RSV组基本一致。RSV+LPS组BALF中细胞总数较LPS组、RSV组增加,且RSV组以淋巴细胞为主,RSV+LPS组以中性粒细胞为主。LPS组、RSV组、RSV+LPS组肺组织炎症及评分均较对照组明显增高。RSV+LPS组AHR较RSV组、LPS组增高。RSV+LPS组肺组织中TRIF表达较LPS组、RSV组增高,各组MyD88基本无变化。RSV组BALF中IFN-γ明显增高,RSV+LPS组KC明显增高,IL-1β、IL-6各组基本无变化。结论 LPS刺激可通过TRIF-KC途径加重RSV感染小鼠气道炎症及AHR。

【Abstract】 The present study was performed to investigate the effects of lipopolysaccharide(LPS) on airway inflammation and hyper-responsiveness induced by respiratory syncytial virus(RSV) infection and the underlying mechanism.Female Balb/c mice(6-8 weeks old) were divided into 4 groups:control,LPS group,RSV group,and RSV+LPS group.Seven days after the first treatment,viral copy number in lung was detected by Q-PCR;infiltration of inflammatory cells in bronchoalveolar lavage fluid(BALF),lung tissue damage as well as AHR were assessed;the expressions of TRIF and MyD88 in the lung tissue were measured by Western blotting,and the concentrations of IFN-γ,KC,IL-1β,and IL-6 in BALF were detected by ELISA.Result showed that viral copies of RSV in RSV+LPS group and RSV group were similar;the influx of leukocytes were remarkably higher in the RSV+LPS group than that of other groups,and the infiltrating cells were lymphocytes-dominant in the RSV group while neutrophilsdominant in the RSV+LPS group;lung tissue damage was significantly increased in LPS group,RSV group and RSV+LPS group,as compared to control;AHR in the RSV+LPS group was higher than that of LPS group and RSV group.The expression levels of TRIF in RSV+LPS group were higher than that in LPS group and RSV group;while levels of MyD88 showed no difference among the 4 groups.IFN-γ was markedly higher in the RSV group in contrast to other groups,while KC was significantly higher in the RSV+LPS group.There were no differences of IL-1β and IL-6 among the 4 groups.In conclusion,LPS could aggravate airway inflammation and AHR induced by RSV through the TRIF-KC signaling pathway.

【关键词】 RSVLPS气道炎症AHR
【Key words】 Respiratory syncytial virusLipopolysaccharideAirway inflammationAHR
【基金】 国家自然科学基金面上项目(81170010);2010年博士点基金新教师类课题(20105503120003)
  • 【文献出处】 免疫学杂志 ,Immunological Journal , 编辑部邮箱 ,2014年10期
  • 【分类号】R363
  • 【被引频次】7
  • 【下载频次】237
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