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Vitamin D improves pulmonary function in a rat model for congenital diaphragmatic hernia.

Abstract：

:A congenital diaphragmatic hernia (CDH) is an anomaly caused by defects in the diaphragm; the resulting limited thorax cavity in turn restricts lung growth (pulmonary hypoplasia). This condition is related to pulmonary hypertension. Despite advances in neonatal CDH therapy, the mortality for severe pulmonary hypoplasia remains high. Therefore, it is essential to establish prenatal therapeutic interventions. Vitamin D was reported to have beneficial effects on adult pulmonary hypertension. This study aims to evaluate the efficacy of prenatal vitamin D administration for CDH. First, serum 25-hydroxyvitamin D [25(OH)D] levels in umbilical cord blood were evaluated among CDH newborns. Second, Sprague Dawley rat CDH models were exposed to nitrofen on embryo day 9 (E9). Randomly selected rats in the nitrofen-treated group were infused with calcitriol from E9 to E21. Samples from CDH pups diagnosed after birth were used for lung weight measurements, blood gas analysis, and immunohistochemical analysis. Third, microarray analysis was performed to examine the effect of vitamin D on gene expression profiles in CDH pulmonary arterial tissues. Serum 25(OH)D levels in the umbilical cord blood of newborns who did not survive were significantly lower than those who were successfully discharged. Prenatal vitamin D showed no significant effect on CDH incidence or lung weight but attenuated alveolarization and pulmonary artery remodeling accompanied the improved blood gas parameters. Vitamin D inhibited several gene expression pathways in the pulmonary arteries of CDH rats. Our results suggest that prenatal vitamin D administration attenuates pulmonary vascular remodeling by influencing several gene pathways in CDH.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Ito Y,Tsuda H,Imai K,Miki R,Miura M,Tachi A,Tano S,Hirako-Takamura S,Moriyama Y,Ushida T,Kobayashi T,Sumigama S,Kajiyama H,Kikkawa F,Kotani T

doi

10.1016/j.abb.2021.108769

subject

Has Abstract

pub_date

2021-01-20 00:00:00

pages

108769

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(21)00019-9

pub_type

杂志文章

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