Effects of vascular endothelial growth factor inhibitor on lung function in mice after unilateral pneumonectomy

Abstract

Objective \nTo investigate the effect of vascular endothelial growth factor (VEGF) inhibitor on lung function in mice after unilateral pneumonectomy. \n \n \nMethods \n45 male C57BL/6 mice undergoing left pneumonectomy were divided into 0 μ g/kg (control group), 5.0 μ g/kg group, 20 μ g/kg group, 60 μ g/kg group and 180 μ g/kg group according to the injection dose of VEGF receptor 1. The daily dosage of each group were 0, 5.0, 20, 60, 180 μg/kg, After 4 days of feeding, the lung volume, lung volume and lung compliance were compared, and the expression of VEGF was further compared, and the expression of hypoxia-inducible factor (HIF) and its related genes were analyzed. \n \n \nResults \nThe VEGF receptor 1 pharmacokinetic model was fitted to a two-compartment model: C=A1 e(-Ke t) + A2 e(-Kα t) + A3 e(-Kβ t). The half-life of VEGF receptor 1 [t1/2 (K)] is 25.997 h; Observed 4 days after surgery, the lung volume value of the 20 μg/kg group was the largest [(64.8±5.1) μl/g]. Compared with the control group (0 μg/kg), the right lung volume of the mice in the 5 μg/kg groups was significantly lower (P<0.05), while the right lung volume in the 60 μg/kg group and the 80 μg/kg group did not obvious change. The right lung volume, total volume and compliance of the mice in the 20 μg/kg group were significantly higher than those in the control group (t=6.568, 11.436, 9.391, P<0.05). Compared with the control group, the expression of VEGFr2 and VEGF mRNA in the 20 μg/kg VEGFr1 group was significantly increased (t=7.425, 9.391, P<0.05). The VEGF content in the lung and plasma of 20 μg/kg VEGFr1 mice was significantly higher than that of the control group (t=23.764, 6.972, P<0.05); (6) The expression of HIF-2α and the expression of HIF-related genes PH, VHL, CXCR4, HK, PDK and PDGFα in the 20 μg/kg group were significantly higher than those in the control group (t=6.486, 12.283, 12.283, 5.134, 12.671, 8.870, P<0.05). \n \n \nConclusion \nVEGF inhibitor can effectively promote the growth of right lung after left lung resection in mice by stimulating HIF at a concentration of 20μg/kg. \n \n \nKey words: \nVascular endothelial growth factor;\xa0Inhibitor;\xa0Mouse;\xa0Unilateral pneumonectomy;\xa0Lung function