[The effect of a vascular endothelial growth factor receptor inhibitor on airway inflammation and airway remodeling in a murine model of asthma].
OBJECTIVE
To investigate the expression of vascular endothelial growth factor (VEGF) and the effect of a VEGF receptor inhibitor on airway inflammation and remodeling in a murine model of asthma.


METHODS
BALB/c mice were randomly divided into three groups: group A (control group, n = 10), group B (asthmatic model group, n = 10) and group C (VEGF receptor inhibitor group, n = 10). The asthmatic model was established by OVA sensitization and challenge. Bronchoalveolar lavage fluid (BALF) cell count and differential were carried out, VEGF levels in BALF and 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 was analyzed with immunohistochemistry (ISH). The airway wall thickness (WAt/Pi), the bronchial smooth muscle thickness (WAm/Pi), the bronchial smooth nucleus counts (N/Pi) and vascular counts were measured by using image analysis system.


RESULTS
There was a significant increase in the numbers of total cells and eosinophils (EOS) in the BALF of group B [(142 +/- 63) x 10(7)/L, 98.0 +/- 46.9 compared to those of group A (30 +/- 14) x 10(7)/L, 0.7 +/- 1.1, all P < 0.01]. After administration of the VEGF receptor inhibitor, the numbers of total cells and EOS were significantly decreased [(41 +/- 17) x 10(7)/L, 4.9 +/- 3.5, all P < 0.01]. BALF and serum levels of VEGF in group B were [(55 +/- 26) pg/ml, and (72 +/- 26) pg/ml] respectively. They were significantly higher than those in group A [(37 +/- 9) pg/ml, (49 +/- 18) pg/ml, respectively] and in group C [(34 +/- 3) pg/ml, (43 +/- 19) pg/ml, respectively]. ISH showed that expression of VEGF in group B was increased compared with group A and C. WAt/Pi, WAm/Pi, and N/Pi in group B [(17 +/- 5) microm(2)/microm, (6.3 +/- 2.2) microm(2)/microm, (0.050 +/- 0.020)/microm, respectively] were all significantly higher than those in group A [(8 +/- 3) microm(2)/microm, (3.2 +/- 0.8) microm(2)/microm, (0.027 +/- 0.017)/microm respectively, P < 0.01 and P < 0.05]. The vascular count of the airways in group B (19 +/- 3) was significantly increased compared to that of group A (10 +/- 5, P < 0.01). Administration of the VEGF receptor inhibitor reduced WAm/Pi (4.5 +/- 1.3) microm(2)/microm, P < 0.05) and the vascular count (11 +/- 3, P < 0.01).


CONCLUSIONS
VEGF was over-expressed in the murine model of asthma, and involved in angiogenesis and airway remodeling. VEGF receptor inhibitors may be effective in reducing allergic airway inflammation and airway remodeling.
Wang
Zhi-hong
ZH
Department of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China.
Lin
Jiang-tao
JT
Nong
Ying
Y
Zhou
Tong-liang
TL
D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D007249:Inflammation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D040262:Receptors, Vascular Endothelial Growth Factor