VEGF与其受体2在哮喘大鼠气道中表达变化及其对气道平滑肌细胞增殖的影响

CORRELATION OF AIRWAY SMOOTH MUSCLE CELLS PROLIFERATION WITH EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND ITS RECEPTOR 2 IN LUNG TISSUES OF ASTHMATIC RATS

目的探讨血管内皮生长因子(VEGF)及其受体2(Flk-1)在哮喘大鼠气道中表达变化及其对气道平滑肌细胞增殖的影响。方法SD大鼠18只,随机分为对照组,哮喘模型组和地塞米松干预组各6只。以腹腔注射1%卵蛋白致敏和2%卵蛋白雾化吸入激发复制哮喘模型,干预组在每次激发前给予地塞米松干预。用免疫组织化学技术检测气道平滑肌αactin以及VEGF和Flk-1蛋白质在不同组大鼠肺组织的表达程度;用RTPCR方法检测VEGF和Flk1mRNA在不同组大鼠肺组织的表达程度;采用HMIAS2000型高清晰度彩色医学图文分析系统进行图像分析。结果(1)哮喘模型组气道壁平滑肌厚度较对照组和干预组显著增加(P<0.05)。(2)哮喘模型组VEGF及Flk-1蛋白质在大鼠肺组织中的表达较对照组和干预组显著增加(P<0.05)。(3)哮喘模型组VEGF144,VEGF188mRNA和VEGF205mRNA在大鼠肺组织中的表达较对照组和干预组显著增加(P<0.05或P<0.01)。哮喘模型组Flk1mRNA在大鼠肺组织中的表达较对照组和干预组显著增加(P<0.05)。直线相关性分析显示,气道壁平滑肌厚度与大鼠肺组织中VEGF205,188,144及Flk-1mRNA表达水平呈正相关(r分别为0.739,0.747,0.744,0.682;P<0.05);气道壁平滑肌厚度与大鼠肺组织中VEGF及Flk-1蛋白质表达水平也呈正相关(r分别为0.693,0.672;P<0.05)。

Objective To investigate the correlation of the airway smooth muscle cells’proliferation with the expression of vascular endothelial growth factor(VEGF) and its receptor 2 (Flk-1) in the lung tissues of asthmatic rats. Methods Eighteen SD rats were randomly divided into three groups: the control group, the asthma model group and the dexamethasone group. The asthmatic model was established by sensitization and challenge with ovalbumin, and the rats in the dethamethasone group inhaled dexamethasone before the challenge. Immunohistochemistry and RT-PCR were used to measure the level of VEGF,its receptor 2 protein and mRNA in the rats’ lung tissues. The thickness of the airway smooth muscle was estimated by a computerized digital image analyzer. Results (1) The thickness of the airway smooth muscle in the asthma model groupwas higher than that in the other groups (P<0.05). (2) The expression of VEGF and Flk-1 protein in the lung tissues of the asthma model group was higher than that in the other groups (P<0.05). (3) The expression of VEGF205,188,144mRNA and Flk-1mRNA in the lung tissues of the asthma model group was higher than that in the control group and the dexamethasone group (P<0.05 or P<0.01). (4) VEGF205, 188, 144 and Flk-1 mRNA expressions were positively correlated with airway smooth muscle thickness (r=0.739,0.747, 0.744,0.682, respectively). VEGF and Flk-1 protein expression were also positively correlated with airway smooth muscle thickness (r=0.693, 0.672, respectively). Conclusion The expressions of VEGF and Flk-1 were increased in the lung tissues of asthmatic rats and positively correlated with the proliferation of airway smooth muscle.VEGF and Flk-1 may take part in the process of airway smooth muscle proliferation in the airway remodeling of asthma.