二苯乙烯化合物Vam3对哮喘小鼠气道炎症以及ICAM-1、NF-κB和MMP-9活性的影响  

Effects of dihydroxy-stilbene compound Vam3 on airway inflammation,expression of ICAM-1,activities of NF-κB and MMP-9 in asthmatic mice

作　　者：杨莉[1] 姚春所[1] 吴志远[2] 玄玲玲[1] 白金叶[1] 程桂芳[1] 林茂[1] 温明春 侯琦[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050 [2]中国医学科学院肿瘤医院肿瘤研究所,北京100021 [3]潍坊哮喘病医院,山东潍坊261041

出　　处：《药学学报》2010年第12期1503-1508,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30772579);山东省自然科学基金资助项目(2007c19)

摘　　要：研究二苯乙烯化合物Vam3对哮喘小鼠肺部黏附分子(ICAM-1)表达和核转录因子(NF-κB)与基质金属蛋白酶(MMP-9)活性的影响。采用卵白蛋白诱导的小鼠哮喘模型,HE染色观察肺组织病理变化,Western blotting方法检测肺组织匀浆中ICAM-1表达的变化,免疫组织化学方法检测肺组织中ICAM-1的表达和分布,荧光素酶报告基因实验检测Vam3对LPS、TNF-α、PMA刺激瞬时转染NF-κB的A549细胞NF-κB活性的作用,明胶酶谱法检测Vam3对LPS、TNF-α、PMA诱导THP-1细胞表达MMP-9活性的影响。结果显示,Vam3对哮喘小鼠肺部炎症细胞浸润、支气管上皮细胞增生脱落、管腔黏液分泌物增多等症状有显著的改善作用,可显著降低肺部ICAM-1的表达。Vam3对LPS、TNF-α、PMA诱导NF-κB的活性有显著的抑制作用。此外,Vam3可抑制LPS、TNF-α、PMA诱导THP-1细胞MMP-9活性。结果显示,Vam3通过降低肺部ICAM-1的表达,下调NF-κB的活性以及抑制MMP-9活性,减轻哮喘炎症反应。The aim of the present study is to investigate the effects of Vam3 which is one of the dihydroxy-stilbene compounds on expressions of ICAM-1 in the lungs of OVA-induced asthmatic mice and the mechanisms of anti-airway inflammation.Balb/c mice were challenged with OVA inhalation.Lung tissues were stained with Mayer’s hematoxylin and eosin for histopathologic examination.The expression of ICAM-1 in the lungs of mice was analyzed by Western blotting and immunohistochemistry method.The NF-κB activities were detected by NF-κB-luc reporter genetic transient transfection method.The activities of MMP-9 induced by LPS,TNF-α and PMA in THP-1 cells were determined by gelatin zymography method.The results showed that Vam3 couldinhibit the expression of ICAM-1 in the OVA-induced mouse model.In addition,Vam3 could significantly suppress the activities of NF-κB in A549 cells and MMP-9 in THP-1 cells induced by LPS,TNF-α and PMA.These results suggested that Vam3 could alleviate the asthmatic inflammation by decreasing ICAM-1 expression in asthmatic mice,down regulating NF-κB and MMP-9 activities.Compound Vam3 showed inhibitory effects on inflammatory signal pathways involved in asthma.

关 键 词：Vam3 哮喘炎症 ICAM-1 MMP-9 

分 类 号：R963[医药卫生—微生物与生化药学]