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Background: The lung is prone to being attacked by intrinsic/extrinsic factors and lung injury is formed. With the increased survival rate of very low birth weight, extremely low birth weight infants, respiratory failure and mortality rate caused by lung development arrest and dysplasia have increased accordingly. This study was designed to investigate the role of insulin-like growth factors (IGFs) in lung development of neonatal rats and effect of dexamethasone (DEX) and retinoic acid (RA) on their expression.
Methods: Eighty timed pregnant Sprague-Dawley rats were randomly divided into 4 groups (n=20): control group (group A), DEX treatment group 1 (group B), DEX treatment group 2 (group C), and RA treatment group (group D). Groups A, B and D were injected subcutaneously with normal saline, intraperitoneally with DEX and RA, respectively on gestational day 18-20; group C was injected subcutaneously with DEX on postnatal day 1-3. Lung tissues were collected at the following time points: gestational day 18, 20, 21 and postnatal day 1, 3, 5, 7, 10, 14, 21 respectively for histopathological examination and expression level determinations of IGF-I, IGF-II polypeptides and mRNA.
Results: The highest expression level of IGF-I in groups A and D occurred on postnatal day 5-7. There was a positive correlation between IGF-I and alveolar development. The highest expression level of IGF-I in group B was observed on postnatal day 3. The expression level of IGF-I was much higher in group B than in group A from gestational day 18 to postnatal day 3 (P<0.01); but it was significantly lower at other time points (P<0.01). The expression level of IGF-I in group C was lower but it was higher in group D than that in group A at any time points (P<0.01). The peak level of IGF-II expression occurred on gestation day 18 and reduced to trace gradually. No differences were found among all groups in the level of IGF-II expression (P>0.05). RT-PCR showed that the trends of IGF-I, -II mRNA expression in the 4 groups were in parallel with those of their polypeptides.
Conclusions: IGF plays an important role in lung development of neonatal rats and there is a close link between DEX, RA and IGF-I, -II. DEX could restrain but RA could accelerate lung development by influencing the expression of IGF-I, -II.
Key words: dexamethasone; retinoic acid; lung development; insulin-like growth factor
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