Effect Of Retinoic Acid On The Expression Of Keratinocyte Growth Factor And Keratinocyte Growth Factor Receptor In The Injuried Lung Tissue Of Neonatal Rats Exposed To Hyperoxia

OBJECTIVE: To observe the influence of retinoic acid on the lung damage and expression of keratinocyte growth factor(KGF) and keratinocyte growth factor receptor (KGFR)of neonatal rats exposed to hyperoxia.METHOD: Ninety full term neonatal Sprague Dawley(SD)rats were divided randomly into three groups within 24 hours after birth. Group I:air+ normal saline (NS)group;Group II:hyperoxia(85%02)+ NS group;Group III : hyperoxia(85 % 02)+ RA group. RA was injected to group III intraperitoneally(500μg/kg)everyday after birth,while NS was given to group I,Ⅱdaily at the same time as group III. On day 4,7 and 14 after birth,8 rats in each group were killed. Lung radial alveolar counts(RAC) were examined.The levels of KGF and KGFR mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR). The expression of KGF protein in lungs was measured by immunohistochemical method. RESULT: (1)Compared with group I,RACs in group II and III were significantly decreased(P<0.05)after 14 days,but those in group III were significantly higher than those in group II(P<0.05).(2)KGF mRNA expression was increased significantly at day 4 of hyperoxia compared with air-breathing control rats (P<0.05). It began to descend after that. Expression also increased at day 7(P<0.05)and decreased significantly at day 14 of hyperoxia exprosure(P<0.05). At the 4th, 7th and 14th day, the expression of KGF mRNA in hyperoxia(85%02)+ RA group all increased obviously compared with the corresponding hyperoxia(85%02)+ NS group(P<0.05). There was no significantly difference in the expression of KGFR mRNA amomg three groups at the 4th day(P>0.05). Compared with group I , the level of KGFR mRNA decreased significantly after hyperoxia at the 7th and 14th day(P<0.05). RA had no effect on the expression of KGFR mRNA. (3)Immunohistoehemistry for KGF was seen primarily in some alveolus, microvascular endothelia cells,and interstitial cells. The changes of KGF protein level were similar to the those of KGF mRNA expression in all 3 groups.CONCLUSION: RA may facilitate the expression of KGF in the lung , ameliorate the impaired development of lung resulting from hyperxia,and play a protective role in lung development from hyperoxia induced inhibition.