摘要
目的 研究信号转导子与转录活化子 1(STAT 1)在支气管哮喘 (简称哮喘 )中的表达及STAT 1对哮喘气道炎症调控 ,以探讨STAT 1信号传导途径在哮喘发病机制中的作用。方法 4 8只豚鼠随机分为正常对照组 (A组 ,8只 )、哮喘组 (B组 )和地塞米松预防组 (C组 ,8只 ) ,哮喘组又随机分为B1、B2 、B3 、B4组 (每组各 8只 )。B组与C组用 10 %卵蛋白 (OVA)腹腔注射与雾化吸入诱发豚鼠哮喘发作 ,在激发后 0h、2 4h、72h、5d通过免疫组化测定豚鼠哮喘模型肺组织中STAT 1与胞间黏附分子 1(ICAM 1)表达 ,免疫印迹检测STAT 1磷酸化 ,测定豚鼠哮喘模型支气管肺泡灌洗液 (BALF)中细胞总数、嗜酸粒细胞计数 ,用酶联免疫吸附法检测γ干扰素 (IFN γ)的浓度。结果 A组气道上皮细胞STAT 1与ICAM 1积分吸光度分别为 13± 7、2 1± 8,而哮喘组 (B1～ 4组 )豚鼠在激发各个时间点 (0h、2 4h、72h、5d)其气道上皮细胞STAT 1与ICMA 1的积分吸光度分别为 5 7± 9、136± 14、95± 2 1、6 7±30 ;75± 10、16 6± 17、113± 14、87± 2 1。B1～ 4组与A组比较差异有显著性 (P <0 0 1) ;气道上皮细胞STAT 1积分吸光度变化与嗜酸粒细胞动态变化呈正相关 (r=0 6 5 2 ,P <0 0 1) ;STAT 1积分吸光度与ICMA 1积分吸光度呈正相关 (r=0 5
Objective To study the expression of signal transducer and activator of transcription-1(STAT-1),and to investigate the effect and mechanism of STAT-1 on airway inflammation. Methods Forty-eight guinea pigs were divided randomly into control group (group A,n =8),asthma group(group B) and prevention group (group C,n =8). The guinea pigs in group B were subdivided randomly into groups B_1,B_2,B_3 and B_4 (each n =8). Asthma guinea pig models in group B and group C were set up by intraperitoneal injection and nebulization aspiration of ovalbumin(OVA).Expression levels of epithelial STAT-1 and intercellular adhesion molecule-1 (ICAM-1) were detected by immunohistochemisty,and lung tissue extracts were analyzed for phosphorylation of STAT-1 by western blot. Total cell and eosinophil(EOS) counts were examined,and expression levels of interferon-gamma (INF-γ) were measured by enzyme-linked immunosorbent assay(ELISA) in bronchoalveolar lavage(BAL). Results After challenge,the expression levels of epithelial STAT-1 [(57±9),(136±14),(95±21),(67±30),respectively] and ICMA-1[(75±10),(166±17),(113±14),(87±21),respectively] in groups B_ 1-4 were significantly different from those in group A[(13±7),(21±8), P <0.01]. The expression levels of epithelial STAT-1 (25±7) and ICMA-1 (29±11) in group C were also significantly different from those in group B_4( P <0.01). The phosphorylation of STAT-1 was found in lung extracts from groups B_ 1-3 . The dynamic changes of STAT-1 was correlated with that of EOS counts,and a positive correlation being observed( r =0.652, P <0.01). There was a significant correlation between epithelial STAT-1 and ICAM-1( r =0.556,P <0.001). A negative correlation was found between epithelial levels of the STAT-1 and levels of INF-γ in BALF ( r =-0.499, P < 0.05) from group B_ 1-4 . Conclusion Epithelial STAT-1 showed constitutive activation and excess expression in guinea pig asthma models,which was significantly correlated with airway inflammation,suggesting that STAT-1 may play an important role in airway inflammation and asthma treatment.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2004年第5期306-310,共5页
Chinese Journal of Tuberculosis and Respiratory Diseases
关键词
支气管哮喘
豚鼠
气道上皮细胞信号转导子
转录活化因子1
表达
气道炎症
调控
Asthma
Epithelial cells
Airway inflammation
Signal transducer and activator of transcription-1
Intercellular adhesion molecule-1
