The Effect of Losartan on Lung Fibrosis of Hyperoxia Induced Newborn Rat CLD

Objective To evaluate the influence of losartan,angiotensin II type 1 receptor(AT1R)antagonists,in a mouse model of hyperoxia-exposed newborn rats induced chronic lung disease(CLD).Methods Within 24 hours after birth,neonatal Wistar rats were divided randomly into four groups:air group(Ⅰ),O2 exposed group(Ⅱ),O2 exposed + aqua(Ⅲ),O2 exposed + losartan(Ⅳ).Except group Ⅰ,neonatal Wistar rats were exposed to about 85%～90% oxygen;from the 6 d after birth to the end of experiment,the pups in group Ⅲ and Ⅳ received aqua and losartan(5 mg/kg)by intragastric administration daily.Pups in each group were sacrificed on 1,3,7,14 and 21 d after the birth.Lung histological changes and degree of collagen fiber in the lungs were evaluated by Hematoxylin eosin and Masson stain.The protein and mRNA level of collagen Ⅰ assayed by ELISA and RT-PCR.Results Neonatal rats exposed to hyperoxia environment resulted in the quantity of alveolar reduced,enlarged terminal air space,secondary septum decreased,and alveolar septa was thicker;alveolar septum was thinner in group Ⅳ comparing with group Ⅱ,but alveolar space was not deflate obviously,and the sum of secondary septum is still less.Neonatal rats exposed to hyperoxia environment caused blue fibres deposition increased markedly.In group Ⅳ,the ratio of blue fibres is decreased and rarefied relatively compare with group Ⅱ,but it is more than group Ⅰ.In group Ⅱ～Ⅳ,collagenⅠprotein and mRNA levels were gradually increased with increasing age(P 0.01),on 21 day up to the peak level.Group Ⅳ decreased slightly on 14 day compared with group Ⅱ,and on 21 day decreased significantly(P 0.01),but still higher than the groupⅠ(P 0.05).Conclusion Losartan attenuated lung collagen deposition of hyperoxia induced newborn rats with CLD,but it does not reverse the hyperoxia-induced neonatal rat lung development block.Losartan does not prevent the occurrence of hyperoxia-induced CLD.