文章摘要
戴 建,殷凯生,孙培莉.咪喹莫特对哮喘小鼠气道反应性及气道重塑的影响[J].南京医科大学学报,2009,29(1):50~54
咪喹莫特对哮喘小鼠气道反应性及气道重塑的影响
Effects of imiquimod on airway hyperresponsiveness and airway remodeling in an asthmatic mouse model
投稿时间:2008-05-20  
DOI:10.7655
中文关键词: 哮喘  咪喹莫特  气道重塑  血管内皮生长因子
英文关键词: asthma  airway remodeling  VEGF  imiquimod
基金项目:国家自然科学基金资助(30570797)
作者单位
戴 建 南京大学医学院附属鼓楼医院呼吸科,江苏 南京 210008 
殷凯生 南京医科大学第一附属医院呼吸科,江苏 南京 210029 
孙培莉 南京医科大学第一附属医院呼吸科,江苏 南京 210029 
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中文摘要:
      目的:观察咪喹莫特对哮喘小鼠气道反应性,气道重塑和肺组织血管内皮生长因子(VEGF)表达的影响?方法:30只小鼠按随机数字表法分成3组,每组10只?正常对照组?哮喘组?咪喹莫特组?小鼠于第0?14天以鸡卵白蛋白(OVA)致敏,第24天开始雾化吸入1%OVA激发并持续28天,建立哮喘气道重塑模型,咪喹莫特组在吸入OVA前2 h雾化吸入咪喹莫特30 min?于最后一次雾化结束后24 h,利用肺功能仪测小鼠气道阻力;收集支气管肺泡灌洗液(BALF)进行细胞计数及分类;对肺组织切片行HE染色观察病理学改变;运用医学图像分析软件测定肺组织切片中的血管计数?血管壁平滑肌厚度?血管壁平滑肌细胞计数;用免疫组化方法检测肺组织VEGF的蛋白表达水平;用RT-PCR检测肺组织VEGF mRNA表达水平?结果:哮喘组小鼠呼气阻力(Re)高于对照组(P < 0.05),咪喹莫特组Re低于哮喘组(P < 0.05);哮喘组BALF中细胞总数及各种炎症细胞数均较对照组升高(P < 0.05),咪喹莫特组较哮喘组降低(P < 0.05);哮喘组血管计数?血管壁平滑肌细胞计数较对照组增高,差异均有统计学意义(P < 0.05),咪喹莫特组血管计数较哮喘组下降,差异有统计学意义(P < 0.05);对照组VEGF蛋白和mRNA在气道不表达或轻度表达,哮喘组VEGF蛋白和mRNA表达较对照组增加,差异有统计学意义(P < 0.05),咪喹莫特组能减少VEGF蛋白和mRNA的表达, 与哮喘组比较差异有统计学意义(P < 0.05),但较对照组仍增加,差异无统计学意义(P > 0.05)?结论:早期预防性雾化吸入咪喹莫特通过部分抑制哮喘肺组织VEGF蛋白和mRNA 的过度表达,阻止慢性哮喘小鼠的血管生成,可在一定程度上减轻哮喘小鼠的气道重塑和气道高反应性?
英文摘要:
      Objective:To observe the effects of imiquimod on airway hyperresponsiveness, airway remodeling and the expression of vascular endothelial growth factor(VEGF) in an asthmatic mouse model. Methods:Mice were randomly divided into a control group(A group), an asthmatic group(B group) and an imiquimod group(C group), each in ten. Mice were sensitized on days 0 and 14 by OVA and challenged from days 24 to 51 by OVA repeatedly to establish a chronic asthmatic model. C group were interfered with aerosol Imiquimod 30 min before challenge. A group was treated with saline instead of OVA. The airway resistance(Re) was measured with pulmonary function meter. Bronchial alveolar lavage fluid was performed and cell differential was examined by Wright-Giemsa staining; the vascular counts were measured by image analysis system. The protein expression of VEGF was determined by immunohistochemistry. The mRNA expression of VEGF was detected by RT-PCR. Results:Re of B group was higher than A group(P < 0.05), Re of C group was reduced compared with B group(P < 0.05). Total cell counts, EOS and lymphocyte in B group were higher than those in A group(P < 0.05),while decreased in C group(P < 0.05). in B group, the expressions of VEGF and mRNA increased when compared with A group(P < 0.05),and decreased in C group(P < 0.05). Conclusion:The experimental data suggest that imiquimod aerosol inhalation may inhibit airway hyperresponsiveness and airway remodeling, decrease the protein and mRNA expressions of VEGF in a mouse model of chronic asthma.
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