Effect Of Leukotriene Receptor Antagonists On Vascular Endothelial Growth Factor And Its Receptors In 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 and its receptors.Methods:Thenty-four male Sprague-Dawley rats were randomly divided into three 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 in three groups were measured by animal lung function meter. Bronchoalveolar lavage fluid cell count and differential were carried out.VEGF levels and Leukotriene D4(LTD4) in serum were measured by enzymelinked-immunosorbent assay(ELISA). The pathologic changes of bronchi and the lung tissue were evaluated, and the VEGF expression and its acceptors were analyzed with immunohistochemistry.The vascular counts and vascular smooth muscle thickness were measured by using image analysis system. The albumen in BALF and serum were measured to calculate the vascular permeatbility index. Results : (1)There was a significant increase in the numbers of total cells and eosinophils in the BALF of asthma group {(128±6)×105/L,(32.55±2.09)×105 /L }compared to those of control group{(42±7)×105/L,(3.28±0.37)×105/L },after administration of the MK the number of total cells and EOS were significiantly decreased{(78±5)×105/L,(8.63±0.18)×105/L } (2) Results of pulmonary function observation: the basic resistance of expiration was not significantly different among three groups, the average expiratory resistance increased remarkbly after inject Ach(P<0.05)(3) The levels of VEGF and LTD4 in asthmatic group serum were 31±6, 10.7±3.5 respectively ,they were significantly higher than those in control group(17±5,6.1±0.7)respectively and in MK group(15.06±4.02,9.8±1.6) respectively.(F=63.78,39.56 P<0.01 (4) Immunohistochemistry showed the expression of VEGF, VEGFR1 and VEGFR2 in asthmatic group were great than that of control and treated group . (5) The vascular counts were 14±2,22±2,16±4 in the control, the asthma, the treated group separately.(6) In asthmatic group the levels of VEGF in serum were positively correlated with the vascular counts (r=0.705, P﹤0.05). In control group the protein expression of VEGF were positively correlated with that of VEGFR1 (r=0.655 p﹤0.05) ,and in asthmatic group the protein expression of VEGF were positively correlated with that of VEGFR2(r=0.731 p﹤0.05),and the ratio of VEGFR1 and VEGFR2 was increased compared with control group.(7)The vascular permeatbility index in three groups were 0.04±0.02,0.16±0.03,0.06±0.02 in the control,the asthma, the treated group separately.Conclusitions: 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.