Expression changes of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 and nuclear factor etythroid-2 related factor 2 and their significance in lung tissues of hyperoxia-induced premature newborn rats / 中华实用儿科临床杂志

ABSTRACT

Objective To observe the expressions of long noncoding RNA (IncRNA)metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and nuclear factor etythroid-2 related factor 2 (Nrf2) in lung tissues of hyperoxia-exposed premature neonatal rats,and explore the role of MALAT1 and Nrf2 in hyperoxia-induced lung injury.Methods Pregnant Sprague-Dawley (SD) rats were given cesarean section on the 21st day of gestation.After feeding for 24 h,a total of 80 premature rats were randomly divided into the air group and hyperoxia group.The rats in the air group were fed in the indoor environment[fraction of inspiration O2 (FiO2) =210 mL/L] and those in the hyperoxia group were fed in a high-oxygen box (FiO2 ＞ 850 mL/L).Eight premature rats from each group were sacrificed and lung tissue samples were collected at 5 experimental time points (1st,4th,7th,10th,14th day),respectively.Hematoxylin-eosin staining was used to observe pathological changes in lung tissues.Real-time quantitative polymerase chain reaction (qPCR) and Western blot were used to detect the expression level of MALAT1and Nrf2.Results Compared with the air group,the degree of alveolarization in lung tissues of the hyperoxia group rats was reduced,and radial alveolar count (RAC) decreased on the 1st day,but there was no significant difference between 2 groups (P ＞0.05),when they decreased on the 4th(3.14 ± 0.23),7th(5.25 ± 0.38),10th (4.41 ± 0.44),14th (3.41 ± 0.13) day of exposure,the differences were statistically significant (all P ＜ 0.05).Compared with the air group,the RNA expression of MALAT1 of hyperoxia group preterm rats decreased after the 1 st day(0.527 ± 0.124) of exposure,increased after the 4th (0.538 ±0.128),7th (0.748 ±0.071) day,decreased after the 10th (0.519 ± 0.081)day,and the differences were statistically significant (all P ＜ 0.05),but it continually became weak on the 14th day,but there was no significant difference between 2 groups (P ＞ 0.05).Compared with the air group,the mRNA expression of Nrf2 of hyperoxia group preterm rats decreased after the 1st day(0.791 ± 0.031) of exposure,increased after the 4th (0.977 ± 0.189),7 th (1.369 ± 0.100),10th (1.094 ± 0.104) day,and the differences were statistically significant (all P ＜ 0.05),and it decreased after the 14th day,but there was no significant difference between 2 groups (P ＞0.05).The hyperoxia group had significantly higher expression of free Nrf2 protein and lower expression of Nrf2-Keapl protein than those of the air group at all time points.Within the hyperoxia group,the RNA expression of MALAT1 was positively correlated with RAC and Nrf2 (r =0.517,0.533,all P ＜ 0.001).Conclusions Lung injury is gradually aggravated over the time of hyperoxia exposure.The level of lncRNA MALAT1 is associated with the severity of lung injury and the level of Nrf2 mRNA,suggesting that IncRNA MALAT1 and the Nrf2 target gene signaling pathway might be involved in the development of hyperoxia-induced lung injury in neonatal premature rats together.