ABSTRACT
Objective:To investigate the effect of Budesonide (BUD) on pulmonary vascular development and the expression of vascular endothelial growth factor (VEGF) and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) in newborn rats with bronchopulmonary dysplasia (BPD) caused by intrauterine infection.Methods:The 15-day-pregnant SD rats were divided into control group and infection group [intraperitoneal injection of 0.35 mg/(kg·d) lipopolysaccharide], and the newborn rats born by the above groups were divided into 3 groups: BUD group (0.5 mg of BUD suspension), normal control group (NC group, equal amount of 9 g/L saline), BPD group (equal amount of 9 g/L saline), with 40 rats in each group, all of them were inhaled twice a day for 14 days.Ten newborn rats were selected at birth, on the 3 rd, 7 th and 14 th day after administration.Pulmonary histopathological changes and radial alveolar counts (RAC) were observed after HE staining, and the thickness of alveolar respiratory membrane was measured; the platelet-endothelial cell adhesion molecule (PECAM-1/CD 31) in lung tissue was detected by immunohistochemistry, and the density of pulmonary microvessels was calculated; the expressions of VEGF, NLRP3 and Caspase-1 were detected by Western blot; and the levels of serum interleukin( IL)-1β and IL-18 were measured by enzyme-linked immunosorbent assay. Results:With the increase of day-old, the lung tissue of newborn rats in NC group was gradually developed and matured, the structure of alveoli was clear, the size was uniform, the count was significantly increased, and no obvious pathological changes were observed.In BPD group, the lung tissue structure was disordered, the alveoli were different in size and few in count, and inflammatory cells were exuded from the alveoli or the alveoli space.Compared with BPD group, the pathological changes of lung tissue in BUD group were significantly reduced.On the 3 rd, 7 th and 14 th day after administration, compared with NC group, the RAC, average integral optical density of CD 31 positive cells, density of pulmonary microvessel and level of VEGF protein in lung tissue of BPD group and BUD group were lower, and the differences were statistically significant (all P<0.05); while the thickness of respiratory membrane, level of NLRP3, Caspase-1 proteins in lung tissue and serum levels of IL-1β, IL-18 were significantly higher, and the differences were statistically significant(all P<0.05). Compared with BPD group, the RAC, average integral optical density of CD 31 positive cells, density of pulmonary microvessel and level of VEGF protein in lung tissue of BPD group and BUD group were significantly higher, and the differences were statistically significant (all P<0.05); while the thickness of respiratory membrane, level of NLRP3, Caspase-1 proteins in lung tissue and serum levels of IL-1β, IL-18 were significantly lower, and the differences were statistically significant (all P<0.05). Conclusions:The occurrence and development of pathological changes of BPD newborn rats caused by intrauterine infection can affect the development of pulmonary vessels through the inflammatory response of lung tissue.BUD can alleviate pathological changes in lung tissues of BPD newborn rats by reducing inflammatory reaction and up-regulating VEGF expression, promoting pulmonary vascular remodeling, and increasing pulmonary microvascular density.