机构地区:[1]广西医科大学第一附属医院儿科,南宁530021 [2]广西医科大学医学实验中心,南宁530021
出 处:《实用儿科临床杂志》2010年第4期242-245,共4页Journal of Applied Clinical Pediatrics
基 金:广西自然科学基金(0991117)
摘 要:目的研究信号转导与转录活化因子3(STAT3)在支气管哮喘(哮喘)小鼠呼吸道中的表达及STAT3与呼吸道重塑的关系,探讨STAT3信号传导途径在哮喘发病机制中的作用。方法Balb/c小鼠30只随机分为正常对照组、哮喘未干预组和AG490干预组,每组各10只。建立鸡卵白蛋白(OVA)致敏的小鼠哮喘模型,HE染色光镜下观察其肺组织结构改变,病理图像分析系统测量其支气管壁厚度(Wat)和平滑肌厚度(Wam),并采用Masson染色观察其肺组织胶原纤维的变化,免疫组织化学染色检测各组小鼠肺组织STAT3表达,免疫印迹法检测磷酸化STAT3(p-STAT3)水平。应用SPSS13.0软件进行统计学分析。结果1.OVA致敏的哮喘模型组小鼠可见支气管壁增厚和管腔狭窄、呼吸道壁周围有大量胶原纤维沉积等呼吸道重塑表现;2.哮喘未干预组小鼠呼吸道上皮细胞STAT3蛋白表达水平、肺组织p-STAT3水平明显高于正常对照组(Pa<0.01,0.05),AG490干预组小鼠肺组织p-STAT3水平、Wat和Wam明显低于哮喘未干预组(Pa<0.05);3.哮喘未干预组小鼠呼吸道上皮细胞STAT3蛋白阳性信号积分吸光度及肺组织p-STAT3水平分别与Wat(r=0.58,P<0.05;r=0.61,P<0.05)、Wam(r=0.46,P<0.05;r=0.53,P<0.05)呈正相关。结论呼吸道重塑是哮喘的基本病理学特征,哮喘小鼠呼吸道上皮细胞STAT3蛋白表达水平及活化程度增加,其增加水平与呼吸道重塑程度相关,阻断STAT3的磷酸化可减轻呼吸道重塑程度,上皮细胞STAT3信号通路可能参与呼吸道重塑过程。Objective To study the expression of signal transducers and activators of transcription 3 ( STAT3 ) in airway epithelial cells of asthmatic mouse model and its association with airway remodeling, explore the role of signal - transduction pathway in airway remodeling. Methods Thirty Balb/c mice were randomly divided into normal control group ( n = 10 ), asthma without intervention group ( n = 10 ) and AG490 intervention group( n = 10). The miee were sensitized with ovalbumin to establish the asthmatic model. The histological changes were evaluated by HE staining,total brochial wall thickness(Wat) and smooth muscle thickness(Wam) were measured by image analysis system, the percentages of collagen deposition were detected by Masson's trichromc staining,the expression of STAT3 in airway were detected by immunohistochemistry technique;lung tissue extracts were analyzed for pbosphorylation of STAT3 (p -STAT3 )by Western blot. SPSS 13.0 soft- ware was used to analyze the data. Results 1. The histological changes including airway thickness, airway smooth cell proliferation and excessive collagen deposition in subepithelial aera were found under light microscope in asthmatic mice. 2. The level of STAT3 and p - STAT3 in asthma without intervention group were significantly higher than those in normal control group( Pa 〈0.01,0.05 ) ,the level of p -STAT3 ,Wat and Warn in AG490 intervention group were significantly lower than those in asthma without intervention group (Pa 〈 0.05 ). 3. The level of STAT3 in epithelial of mouse in asthma without intervention had positive correlations with Wat ( r = 0.58, P 〈 0.05 ), Warn ( r = 0.61, P 〈 0.05 ), and the level of p- STAT3 in lung tissue had positive correlations with War (r = 0.46,P 〈 0.05 ) and Wam( r = 0.53,P 〈 0.05 ) ,respectively. Conclusions Airway remodeling is the main pathological changes of chronic asthma, epithelial STAT3 showes excess expression and constitutive activation in asthma models, which is sign
关 键 词:哮喘 呼吸道重塑 信号转导与转录活化子3 上皮细胞
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