Protective mechanism of 1,25-Dihydroxyvitamin D3 on hyperoxia-induced lung injury in neonatal rats

Abstract

Objective To investigate the effects and mechanisms of 1,25-Dihydroxyvitamin D3 [1,25(OH)2 D3] on hyperoxia-induced lung injury of neonatal rats.Methods Neonatal Sprague-Dawley rats were randomly divided into air group,hyperoxia group and 1,25(OH)2D3 group within 12 hours after birth,eight in each group.Rats in air group were exposed to air,while those in hyperoxia and 1,25 (OH) 2 D3 group were exposed to hyperoxia (≥85 ％ oxygen concentration).Rats in 1,25(OH)2D3 group were injected with 1,25(OH)2D3 0.5 μg/(kg · d) intraperitoneally once a dayfor seven days,meanwhile the rats in the other two groups received 0.9 ％ saline in the same way.All rats were sacrificed on day 7.Lung tissue sections were HE stained in order to assess lung histological changes and lung radical alveolar count (RAC).The levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β and IL-6 mRNA were measured by real time-polymerase chain reaction.Analysis of variance and LSD test were applied for statistics.Results Compared with the air group,the weight of rats in the hyperoxia group was significantly lower on day 7 [(8.48±1.34) g vs (12.51±0.47) g,t=8.05,P＜0.05],while the weight of rats in 1,25(OH)2D3 group [(10.29±1.00) g] was higher than that in the hyperoxia group (t=3.61,P＜0.05).Lung tissue structure was normal in the air group.In the hyperoxia group,inflammatory exudation was observed in pulmonary interstitial,the alveolar size was uneven,and the RAC was lower than that in the air group (5.6±0.1 vs 6.8±0.2,t=21.45,P＜0.05).The RAC in 1,25(OH)2D3 group (6.2±0.1) was significantly increased compared with that in the hyperoxia group (t=11.76,P＜0.05),but still lower than that in the air group (t=9.69,P＜0.05).The expressions of TNF-α,IL-1β and IL-6 mRNA in hyperoxia group (0.0348±0.0006,0.0269±0.0003 and 0.0368 ± 0.0006) were higher than those in the air group (0.0111±0.0007,0.0040±0.0003 and 0.0162 ±0.0007,t=56.54,111.12 and 49.26,P＜0.05,respectively).The expressions of TNF-α,IL-1β and IL-6 mRNA in the 1,25 (OH)2D3 group (0.0203±0.0009,0.0141±0.0004 and 0.0251±0.0009) were lower than those in the hyperoxia group (t=34.44,61.93 and 27.99,P＜0.05,respectively),but higher than those in the air group (t=22.10,49.19 and 21.27,P＜0.05,respectively).Conclusions 1,25(OH)2D3 could attenuate hyperoxia-induced lung injury by inhibiting the expression of inflammatory cytokines. Key words: Calcitriol; Hyperoxia ; Acute lung injury; Cytokines ; Animals, newborn; Rats