白三烯受体拮抗剂对致敏大鼠血管内皮生长因子及其受体表达的影响

目的 研究白三烯受体拮抗剂(孟鲁司特)对支气管哮喘(简称哮喘)气道炎症和气道重塑的影响,揭示白三烯受体拮抗剂对血管内皮生长因子(VEGF)及其受体的调控作用.方法 将24只清洁级雄性SD大鼠按随机数字表法分为对照组、哮喘组和干预组,每组8只.对照组采用生理盐水致敏和激发,哮喘组采用卵清白蛋白致敏和激发,干预组在采用卵清白蛋白致敏和激发前给予孟鲁司特灌胃.采用肺功能检测各组大鼠气道呼气阻力;采用酶联免疫吸附法(ELISA)对各组大鼠血清中VEGF和白三烯D<4>(LTD4)进行定量分析;用免疫组织化学方法检测VEGF、VEGF受体1(VEGFR1)及VEGFR:在大鼠肺组织内的表达水平.采用图像分析软件测定肺组织切片中的血管计数、血管平滑肌厚度.结果 (1)肺功能检测显示哮喘组平均呼气阻力显著升高;(2)对照组血清中VEGF和LTD4的水平分别为(17±5)ng/L和(6.1±0.7)ng/L,哮喘组分别为(31±6)ng/L和(10.7±3.5)ng/L,干预组分别为(15±4)ng/L和(9.8±1.6)ng/L,对照组和干预组分别与哮喘组比较差异有统计学意义(F值分别为63.78和39.56,均P<0.01);(3)免疫组织化学结果显示哮喘组VEGF及受体均大量表达,而对照组和干预组有较少表达.(4)图像分析显示,对照组、哮喘组和干预组的血管计数分别为14±2、22±2和16±4.(5)直线相关分析显示,血管计数与血清中VEGF的水平正相关(r=0.705,P<0.05).结论 VEGF及其受体在哮喘气道及肺内过度表达,参与了气道炎症和气道血管重塑的过程.孟鲁司特可能通过影响VEGF及其受体的表达影响气道炎症和气道血管重塑的病理生理过程.

Effects of leukotriene receptor antagonists on vascular endothelial growth factor and its receptors in a sensitized rat model

Objective To investigate the effect of montelukast(MK) on airway inflammation and remodeling in asthmatic rats, and to explore the regulating role of MK on vascular endothelial growth factor (VEGF) and its receptors. Methods Twenty-four male Sprague-Dawley rats were randomly divided into 3 groups, a control group(n =8), an asthmatic group(n =8) and a MK treated group(n =8). The rats were sensitized with ovalbumin and AL (OH3), and repeatedly exposed to aerosolized ovalbumin. Airway reactivity of the animals were measured by animal lung function meter. VEGF levels and leukotriene D4 (LTD4) in serum were measured by enzyme linked-immunosorbent assay(ELISA). The pathologic changes of bronchi and the lung tissue were evaluated, and the expression of VEGF and its receptors was analyzed with immunohistochemistry. The vascular counts and vascular smooth muscle thickness were measured by using image analysis system. Results The bronchial provocation test showed that, in the asthmatic group, the average expiratory resistance increased remarkably. The serum levels of VEGF and LTD4 in the asthmatic group were 31±6 and 11±4 respectively, significantly higher than those in the control group(17±5 and 6.1±0.7)respectively and in the MK group(15±4 and 9.8±1.6) respectively(F=63.78, 39.56, all P<0.01). Immunohistochemistry showed that, the expression of VEGF, VEGFR1 and VEGFR2 in the asthmatic group were increased, as compared to those in the control group and the treated group. The vascular counts were 14±2, 22±2 and 16±4 in the control, the asthmatic, and the treated groups. Conclusions VEGF and its receptors were over-expressed in the sensitized rat model, and involved in angiogenesis and airway remodeling. MK may be effective in reducing allergic airway inflammation and airway remodeling through VEGF and VEGFR.