Effects of intrauterine exposure to ambient fine particles on immune function-related indicators in neonatal rats / 中华围产医学杂志

ABSTRACT

Objective@#To investigate the effects of maternal exposure to ambient fine particles (PM2.5) in Fuzhou during pregnancy on immune responses to ovalbumin (OVA) in neonatal rats and the possible mechanisms.@*Methods@#Pregnant Sprague-Dawley rats were randomly assigned into four groups (ten in each) filtered air (FA) plus normal saline (NS), airborne PM2.5 plus NS (PM2.5-NS), FA plus OVA (FA-OVA) and PM2.5 plus OVA (PM2.5-OVA) groups. Pregnant dams in the PM2.5 exposure groups were placed in a PM2.5 exposure chamber in which the PM2.5 concentration was equal to the ambient air from the beginning of gestation till delivery, whereas the other dams inhaling air without particulate matters were put into a clean chamber. OVA sensitization was conducted through intraperitoneal injection of OVA at 50 μg per dam at 4 and 9 days of gestation, followed by inhalation of atomized 1% OVA for 30 min at 18, 19 and 20 days of gestation. Dams without OVA sensitization were given NS in the same way. Levels of interleukin (IL)-4, IL-5 and interferon-γ (IFN-γ) in neonatal rats' plasma were measured by enzyme-linked immunosorbent assay just after birth. Protein levels of transcription factors GATA-3 and T-bet in lung were analyzed by Western-blotting. Changes in microRNA(miR)-146a and miR-146b in spleen were detected by real-time polymerase chain reaction. Histological changes in lung were observed under light microscope. One-way analysis of variance and LSD test were used as statistical methods.@*Results@#(1) IL-4 level in plasma was significantly increased in PM2.5-NS [(18.56±7.04) ng/L], FA-OVA [(34.04±7.06) ng/L] and PM2.5-OVA groups [(45.67±8.18) ng/L] as compared with that in FA-NS group [(10.51±2.88) ng/L], and the level of IL-4 in PM2.5-OVA group was higher than that in PM2.5-NS and FA-OVA groups (F=54.667, P<0.001). Significantly increased IL-5 level in plasma was found in FA-OVA and PM2.5-OVA groups as compared with that in FA-NS group (F=6.253, P=0.023). Among the four groups, FA-OVA group showed significantly increased IFN-γ level in plasma (F=28.604, P<0.001). (2) GATA-3 level in lung tissues was significantly increased in PM2.5-NS (31.09±3.54), FA-OVA (35.24±5.00) and PM2.5-OVA groups (47.81±3.63) as compared with that in FA-NS group (24.19±3.12), and higher in PM2.5-OVA group than in PM2.5-NS and FA-OVA groups (F=96.581, P<0.001). T-bet level was significantly lower in FA-OVA and PM2.5-OVA groups than in FA-NS group. Moreover, PM2.5-OVA group showed decreased T-bet level as compared with that in PM2.5-NS and FA-OVA groups (F=30.852, P<0.001). (3) Expression of miR-146a in spleen was significantly enhanced in PM2.5-NS (1.72±0.27), FA-OVA (1.56±0.37) and PM2.5-OVA groups (3.06±0.52) than in FA-NS group (1.05±0.25). Moreover, PM2.5-OVA group showed enhanced expression of miR-146a as compared with that in PM2.5-NS and FA-OVA groups (F=42.276, P<0.001). Changes in the expressions of miR-146b were similar to those in miR-146a (F=28.776, P<0.001). (4) Stenosis or disappearance of alveolar spaces, accompanied with infiltration of inflammatory cells in interstitial substance and congestion in alveolar septum, was seen in FA-OVA and PM2.5-OVA groups and conditions in the latter group were more severe.@*Conclusions@#Intrauterine exposure to ambient PM2.5 negatively affects fetal lung development and immunological function in rats, especially when the dams are sensitized with OVA during pregnancy.