维生素D对羊膜腔注射脂多糖导致的新生鼠肺泡化阻滞的作用

Effects of Vitamin D on intra-amniotic lipopolysaccharides-induced alveolarization arrest in neonatal rats

目的探讨维生素D(Vit D)对宫内绒毛膜羊膜炎诱发的肺泡化阻滞的改善作用及可能的机制。方法通过孕鼠羊膜腔注射脂多糖(LPS)建立新生鼠支气管肺发育不良(BPD)模型。分为Saline组、LPS+Saline组、LPS+Vit D(L)组和LPS+Vit D(H)组。Vit D干预的2组新生鼠出生后每日腹腔注射0.5和3 ng/g的1,25(OH)_2D_3,Saline组和LPS+Saline组注射等量生理盐水。取第1、3、7日的新生鼠肺组织,通过苏木精-伊红(H-E)染色观察病理学改变。采用real-time PCR检测IL-1β和IFN-γmRNA表达。结果不同剂量的Vit D均显著提高新生鼠出生率(均P=0.003)。出生后7 d,Vit D干预的2组较LPS+Saline组肺泡计数显著增多(P=0.001,P=0.000),平均内衬间隔显著减少(均P=0.000),且Vit D干预的2组IL-1β和IFN-γmRNA表达显著低于LPS+Saline组(均P=0.000)。结论予以Vit D可降低新生鼠肺部IL-1β和IFN-γ表达,减轻BPD病理学改变。

Objective To investigate the role of Vitamin D （VitD） on amelioration of chorioamnionitis-induced alveolarization arrest and possible mechanisms. Methods A neonatal rat bronchopulmonary dysplasia （BPD） model was constructed by intra-amniotic injection of lipopolysaccharides （LPS） in pregnant rats. Rats were randomly assigned to the Saline group, LPS ＋ Saline group, LPS ＋ VitD （L） group, and LPS ＋ VitD （H） group. Neonatal rats in the LPS ＋VitD （L） group and the LPS ＋VitD （H） group were intraperitoneally injected with 0.5 and 3 ng/g 1, 25（OH）＋ Da respectively once a day for 7 d. Meanwhile, neonatal rats in the Saline group and the LPS ＋ Saline group were intraperitoneally injected with the same volume of normal saline. The pulmonary tissues of neonatal rats were harvested 1, 3, and 7 d after the final injection and were stained by H-E staining for observing pathological changes. The mRNA expressions of IL-1β and IFN-y were detected using real-time PCR. Results Different concentrations of VitD could improve the birth rate of neonatal rats （P = 0. 003）. The LPS ＋VitD （L） group and the LPS ＋VitD （H） group had significantly higher alveolar counts （P=0. 001, P=0. 000）, remarkably decreased mean liner intercept （P =0. 000）, and significantly decreased mRNA expressions of IL-1β and IFN-y as compared with the LPS ＋ Saline group 7 d after birth （P=0. 000）. Conclusion Administration of VitD can significantly decrease the expressions of IL-1β and IFN-7 in lungs of neonatal rats and alleviate the pathological changes of BPD.