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

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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。 To investigate the effect of stilbene compound Vam3 on the expression of ICAM-1 and the activity of nuclear factor-kappa B (NF-κB) and matrix metalloproteinase (MMP-9) in asthmatic mice. The mouse model of asthma induced by ovalbumin was used. The pathological changes of lung tissue were observed by HE staining. The expression of ICAM-1 in lung homogenate was detected by Western blotting. The expression and distribution of ICAM-1 in lung tissue were detected by immunohistochemistry. The luciferase reporter assay was used to detect the effect of Vam3 on the NF-κB activity in LPS, TNF-α, PMA-stimulated A549 cells transiently transfected with NF-κB. Gelatin zymography was used to detect the effect of Vam3 on THP- 1 cells to express MMP-9 activity. The results showed that Vam3 could significantly improve the expression of ICAM-1 in the lungs in asthmatic mice with inflammatory cell infiltration, bronchial epithelial cell proliferation and exudation of lumen mucus. Vam3 significantly inhibited the activity of NF-κB induced by LPS, TNF-α and PMA. In addition, Vam3 can inhibit LPS, TNF-α, PMA-induced MMP-9 activity in THP-1 cells. The results showed that Vam3 reduced the inflammatory response of asthma by decreasing the expression of ICAM-1 in the lung, down-regulating the activity of NF-κB and inhibiting the activity of MMP-9.
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