血管内皮生长因子受体抑制剂SU5614对哮喘模型小鼠气道炎症的影响

Effects of vascular endothelial growth factor receptor inhibitor SU5614 on airway inflammation in mouse models of asthma

目的观察血管内皮生长因子(VEGF)受体抑制剂SU5614对甲苯二异氰酸酯(TDI)诱发哮喘模型小鼠VEGF表达、气道反应性和气道炎症的影响。方法 BALB/C小鼠30只,随机分为3组(n=10):对照组、模型组和SU5614组。采用TDI作为致敏原制备小鼠哮喘模型。SU5614组:SU5614溶解于二甲基亚砜(DMSO)中,于激发1 h后按照2.5 mg/kg给予腹腔注射,每日1次,连续3 d;模型组:只造模,不用药;对照组:未造模小鼠。观察各组小鼠VEGF的表达情况、气道反应性的变化,以及支气管肺泡灌洗液中细胞总数和白细胞分类的变化。结果 Western blotting和免疫组织化学分析结果显示:模型组VEGF表达明显增加,SU5614组则明显降低。模型组气道反应性明显高于对照组,SU5614组则明显低于模型组,差异具有统计学意义(P<0.05);模型组小鼠支气管肺泡灌洗液中细胞总数以及中性粒细胞、巨噬细胞、淋巴细胞和嗜酸性粒细胞数明显高于对照组,SU5614组则明显低于模型组,差异具有统计学意义(P<0.05)。结论 SU5614可抑制支气管肺泡灌洗液中VEGF的表达,降低气道高反应性,减轻气道炎症。

Objective To observe the effects of vascular endothelial growth factor（VEGF） receptor inhibitor SU5614 on the expression of VEGF, airway inflammation, and airway responsiveness in mouse models of toluene diisocyanate（TDI） induced asthma. Methods Thirty BALB /C mice were randomly divided into 3groups（ n = 10）, i. e. the control group, model group, and SU5614 group. Asthmatic models were established by using TDI as the allergen. For the SU5614 group, SU5614 dissolved in dimethylsulfoxide（ DMSO） was intraperitoneally injected 1 h before challenge with the dose of 2. 5 mg /kg per day for 3 d. For the model group,no medicine was administered before challenge. While for the control group, no medicine was administered and no challenge was conducted.The expression of VEGF, variations of airway responsiveness, and variations of the total cell count and leukocyte differential count in bronchoalveolar lavage fluid of each group were observed.Results Results of the Western blotting and immunohistochemistry analysis showed that the VEGF expression of the model group increased significantly and the VEGF expression of the SU5614 group decreased significantly.The airway responsiveness of the model group was significantly higher than that of the control group and the airway responsiveness of the SU5614 group was significantly lower than that of the model group.The differences were statistically significant（ P 〈0. 05）.The number of total cells, neutrophils, macrophage, tymphocytes, and eosinophils in bronchoalveolar lavage fluid of the model group were significantly higher than those of the control group and those of the SU5614 group were significantly lower than those of the model group.The differences were statistically significant（ P〈 0. 05）. Conclusion SU5614 can inhibit the expression of VEGF in bronchoalveolar lavage fluid, decrease the airway hyperresponsiveness, and relieve the airway inflammation.