Changes Of CXCL8 And Neutrophils In Lung Of Preterm Rats With Hyperoxia-Induced Bronchopulmonary Dysplasia

Objective To investigate histological changes of lung and contents and roles of neutrophil and CXCL8 in alveolus in the course of development bronchopulmonary dysplasia(BPD) by establishment hyperoxia-induced BPD model in preterm rats.Methods(1)120 preterm SD rats(within 6 hours after deliveried by cesarean section at 21 days of gestational age)were divided randomly into two group:experimental group(hyperoxia group,n=60) and control group(air group,n=60).Pups in experimental group were placed in plexiglas chamber and exposed to hyperoxia(FiO₂>95%) with CO₂ was absorbed by sodalime.Pups in control group were raised normally inhaling room air.Temperature and humidity were maintained at 25℃～27℃and 50%～70%respectively in two groups.(2)On 1d,3d,5d,10d,14d of experiment,six pups from each group were sacrificed and performed with lung lavage.Bronchoalveolar lavage fluid was centrifuged at 2000 rpm×5min at 4℃.The supernatant fluid was used for measurement of CXCL8 protein by ELISA.The cell sediment in bottom was suspended in 0.5ml PBS for neutrophil cell counting.Two pups of each group were sacrificed and histological changes(hematoxylin-eosinstain staining) in lungs were observed by light microscope.Results(1)On 1d of experiment,the alveolar structure was irregular in both two groups with terminal air space size was rather small and the alveolar septum was thick.The structure of pulmonary tissue developed to normalized with aged in control group.In hyperoxia group,a few inflammarory cells in interstitial tissue,red blood cells in alveoli,increasing interstitial cells and vasodilatation could be found on 3d and the findings appeared more severe on 5d with thicker alveolar septum and alveolar dilation.On 10d,terminal air space size became larger with less alveoli,more inflammatory cells in alveoli and more interstitial cell with thicker alveolar septum could be found in hyperoxia group.On 14d,more obvious alveolar dilation and simplified structure with less alveolar counts and alveolar fusion with interstitial fibrosis could be found.(2) CXCL8 in BALF increased significantly in hyperoxia group from 3d to 14d compared to age-matched,air-exposed controls,and maintained at high lever till 14d(P<0.01 in each matched groups) but there was no difference betweem tow groups on ld(P>0.05).Counts of PMN in BALF increased significantly in hyperoxia group from 3d to 14d compared to age- matched,air-exposed controls, and reached peaked on 10d(P<0.01 in each matched groups) but there was no difference betweem tow groups on ld(P>0.05).(3)The level of CXCL8 in BALF on 1d to 14d was obviously correlation with PMN count(r=0.564,P<0.05) and was high positive correlation(r=0.931,P<0.01) on 1d to 10d. Conclusion(1)High concentration of oxygen can induce lung injury and which can develop into BPD;(2)The level of CXCL8 and the counts of PMN in BALF increased significantly when exposed to hyperoxia which means that CXCL8 and PMN may contribute to hyperoxia-induced lung injury and BPD;(3)The level of CXCL8 was positive correlation with PMN count during the development of BPD suggests that both CXCL8 and PMN together involved in the formation of BPD and there exists interaction between CXCL8 and PMN.