血管内皮生长因子受体抑制剂SU5614对甲苯二异氰酸酯诱导哮喘模型小鼠治疗作用的研究

Therapeutic effect of VEGF receptor inhibitor SU5614 in a murine model of toluene diisocyanate induced asthma

目的:探讨血管内皮生长因子(VEGF)受体抑制剂SU5614对甲苯二异氰酸酯(TDI)诱导哮喘模型小鼠的治疗作用。方法:BALB/C小鼠随机分为3组:对照组,模型组和SU5614组。采用TDI制备哮喘小鼠模型,观察SU5614对模型小鼠支气管肺泡灌洗液(BALF)VEGF的表达情况、肺组织病理学变化,气道反应性和气道血浆渗出的变化。结果:免疫细胞学分析结果表明,模型组小鼠BALF中VEGF表达明显增加,而SU5614组VEGF表达则明显降低;病理组织学发现模型组肺组织病理学炎症反应明显,而SU5614组炎症反应则明显减轻;模型组气道反应性明显增高,而SU5614组则明显降低(P<0.05);模型组气道血浆渗出明显增加,而SU5614组则明显减少(P<0.05)。结论:SU5614不仅抑制BALF中VEGF活性,也能抑制炎性细胞的迁移,降低气道高反应性和减少气道血浆渗出。

AIM：To discuss the therapeutic effect of vascular endothelial growth factor（VEGF）receptor inhibitor SU5614 in a murine model of toluene diisocynate（TDI）induced asthma.METHODS：BALB/C mice were randomly divided into three groups：the control group,the model group and the SU5614 group.Using the TDI induced asthma in mice,the effect of SU5614 was evaluated on expression of VEGF in bronchoalveolar lavage fluid（BALF）,pathological changes of lung tissue,determination of airway responsiveness to methacholine and measurement of plasma exudation.RESULTS：Immune cytological analysis showed that expression of VEGF in BALF was significantly increased in model group,but significantly decreased in the SU5614 group.The airway inflammation of lung tissue was expressed obviously in model group,but significantly reduced in the SU5614 group.The airway responsiveness increased in model group,while in the SU5614 group it was significantly reduced（P〈0.05）.Plasma exudation was significantly increased in model group,but significantly decreased in the SU5614 group（P 0.05）.CONCLUSION：SU5614 not only inhibit VEGF activity in BALF,but also inhibit the migration of inflammatory cells,reduce airway inflammation and plasma exudation.