小鼠哮喘模型肺组织中STAT1活性变化及其对ICAM1表达的影响_药学论文.doc免费

小鼠哮喘模型肺组织中STAT1活性变化及其对ICAM表达的影响_药学论文 小鼠哮喘模型肺组织中STAT1活性变化及其对ICAM表达的影响_药学论文 【摘要】 目的 探讨信号转导和转录激活子1（signal transducers and activators of transcription 1,STAT1）DNA结合活性在小鼠哮喘模型的肺组织中不同时间点的变化及其对细胞间黏附分子（intercellular adhesion molecule）表达的调控作用。方法 用鸡卵白蛋白(OVA)抗原溶液腹腔注射致敏,雾化吸入激发制备哮喘小鼠模型，造模后凝胶迁移滞留试验（EMSA）的方法测定病变肺组织中STAT1 DNA结合活性在模型组不同时间点(8 h、24 h、48 h、96 h、7 d)的变化；PCR法测定ICAM在上述时间点的表达，设生理盐水对照组。设生理盐水对照组为0 h时间组。结果 造模后肺STAT1明显活化，96 h达到最高峰；ICAM与蛋白表达在8 h开始有所增加，96 h达高峰。STAT1 DNA结合活性及ICAM表达呈高度正相关。对照组则无明显改变。结论 哮喘模型的病变肺组织STAT1 DNA结合活性的持续与异常升高，STAT1参与鸡卵白蛋白诱导的小鼠哮喘的发生和发展；ICAM在模型的不同时间点表达增加，可能受到STAT1调控。 【关键词】 小鼠 鸡卵白蛋白 哮喘 动物模型 转录 黏附分子 　　Abstract:Objective To detect the change of DNAy STAT1 in the mice model with electrophoretic mobility shift assay (EMSA) and PCR. Methods Mice were randomized into different groups: asthma group and normal control group. Mice in model group were sensitized by intraperitoneal injection and Al(OH)3 on 0,14 d. On 18,19,20 d,the animals were challenged with 10 g/L OVA aerosol for 20 min. The models were divided into 6 groups which were killed at 0 h,8 h,24 h,48 h,96 h,7 d. Activity of STAT1 DNAbinding was detected by electrophoresis mobility shift assays (EMSA) at various time points. Expression of ICAM1 was detected by PCR. Results The binding activity of STAT1 increased with a dynamic curve in experimental groups. It began to increase at 8 h point time and reached to peak at 96 h,then decreased but still keep obviously higher at 7 d versus control group (0.01). Levels of ICAM1 mRNA significantly elevated at 8 h and the peak was at 7 d. Conclusions STAT1 activation is an important factor that may be involved in acute and chronic inflammation development. STAT1 also regulated ICAM1 expression during asthma. 　　Key words:mice; OVA; asthma; animal model; transcription; intercellular adhesion molecule 　　支气管哮喘(bronchial asthma,BA)是一种气道非特异性炎症性疾病,在我国发病率比较高，严重影响患者的身心健康和生活质量，给社会及家庭造成了严重的经济负担。随着研究的深入，细胞信号转导途径对哮喘的作用越来越受重视，特别是信号转导和转录激活子1（signal transducers and activators of t