Renal Pathologic Changes And HGF Expression In Neonatal Lung Injury Model Induced By Hyperoxia

The neonatus whose organs are immature especially in premature neonatus are hard to endure ischemia and anoxic and liable to suffer organs damage.Therefore,there are more chances to use oxygen therapy. But prolonged hyperoxia exposure can result in lung injury in different extent,and even develop into chronic lung disease(CLD).Recently, worldwide scholars progressed widely researches in hyperoxia lung injury in animal model.There have been reported on injury of hyperoxia to retina,encephalon,liver and intestines,but seldom on kidney.There are few investigations about the renal dynamic pathologic struction exposing to prolonged hyperoxia.Hepatocyte growth factor(HGF) is a multifunction cytokine,which can stimulate mitosis of epithelial and endothelioid cells,speed morphogenesis of renal tubular,and inhibit cell apoptosis.It has significant effect in the development,acute injure and reparation of kidney.In our study,we base on full-term neonatal rats to found hyperoxia lung injury model,and to research the pathologies of lung and kidney,the apoptosis of kidney cells and the different expression of HGF in kidney during lung injury.We observe the influences of kidney when prolonged hyperoxia lung injury occurs,to intent to provide experiment evidences and prevent proofs on clinical kidney injury during hyperoxia lung injury of newborn.Chap.One The effect of prolonged hyperoxia exposure on pathologies of the neonatal rats kidneyObjective:Exploring the effect of hyperoxia on pathologies of the neonatal rats lung and kidney by observing the changes of lung and kidney histology in neonatal rats exposed to hyperoxia.Methods:The full-term newborn rats were randomly assigned into hyperoxia group(group HO) and Air group(group Air) within postnatal 12 hour(P 12h).The group HO was continuously given a high concentratsion of oxygen(FiO2＞0.90) and the group Air received oxygen with the FiO2 of 0.21.The lung tissue(left) and left ren of two groups were collected,at postnatal 3 day(P 3d),P 7d,P 14d and P 21d, for observing pathologic changes with light microscope by HE staining, and detecting renal apoptosis index(AI) by an in situ end labeling method(TUNEL Staining).Results:①The results of lung tissue using HE staining:Compared with the group Air,exudation of red cells(Eosinophilic Substances) in alveolar cavity and infiltratsion of inflammatory cells in alveolar septum appearring in P 3d of group HO.Alveolar cavities becoming bigger; alveolar walls becoming thinner;and alveolar interstitial cells proliferatsed in P 7d of group HO.Alveolar cavity becoming bigger obviously,some alveolar fused,also alveolar quantity decreased,and alveolar interstitial cells becoming further hyperplasia in P 14d of group HO.Structure of alveolar disappeared,quantity decreased and diameter of alveolar cavity increased significantly,large area alveolar fused,and alveolar septum becoming thinness with a lot of interstitial cells hyperplasia in P 21d of group HO.②The result of ren using HE staining:Compared with the group Air,glomerulus capillary congested, renal capsule becaming narrow in P 3d of group HO.Glomerulus cells proliferatsed(＜25%),mesangial cells proliferatsed,also renal medullae capillary proliferatsed and congested,and there being a little interstitial cells hyperplasia in P 7d of group HO.Glomerulus cells proliferatsed (25%-50%),reversible focal hyalinosis appeared,mesangial cells and renal medullae capillary all proliferatsed and interstitial cells proliferatsed obviously(＞50%),epithelial cells of convoluted tubule proliferatsed and some cell nuclear showed vacuolar degeneratsion in P 14d of group HO.Glomerulus cells proliferatsed significantly, reversible focal hyalinosis appeared,mesangial cells proliferatsed obviousily,little lymphocyte infiltratsed,renal capsule becoming expansion,renal medullae epithelial cells of convoluted tubule proliferatsed,mostly interstitial cells proliferatsed(＞75%),and also red cells exosmosis,nuclear of convoluted tubule hypertrophy with vacuolar degeneratsion,apoptosis and nuclear division occurred in P 21 d of group HO.③The result of renal apoptotic cells:cell apoptosis appeared in each group.The AI were minimum in group Air at P 3d.In group HO, the AI were higher than group Air from P 3d.(group Air,3d 0.06±0.01, 7d 0.27±0.02,14d 0.22±0.06,21d 0.13±0.10;group HO,3d 0.57±0.20, 7d 1.74±0.59,14d 2.77±0.70,21d 1.39±0.55).Campare with group Air, the AI in group HO increased significantly at P 3d,P 7d,P 14d and P 21d(p＜0.01).In group HO,the AI increased gradually with the day old prolonged(F=35.77,p＜0.01),but decreased at P 21 d.Conclusions:①Alveolar development obstacle is the main pathological change of neonatal rats with prolonged hyperoxia exposure.②The proliferatsion of renal mesangial cells and convoluted tubule epithelial cells is the main renal pathological change of neonatal rats model with hyperoxia-induced lung injury.Kidney injury aggravated gradually with the time prolonged hyperoxia exposure.③The proliferatsion of apoptotic renal cells is maybe relevant to the process of renal injury of neonatal rats model with hyperoxia-induced lung injury. Chap.2 The effect of prolonged hyperoxia exposure on HGF expression in neonatal rats kidneyObjective:Observing the dynamic expression of HGF in ren of neonatal rats model with hyperoxia-induced lung injury.Discussing the significance of HGF expression in kidney of the neonatal rats model.Methods:The Full-term newborn rats were randomly assigned into hyperoxia group(group HO) and Air group(group Air) within postnatal 12 hour(P 12h).The group HO was continuously given a high concentratsion of oxygen(FiO2＞0.90) and the group Air received oxygen with the FiO2 of 0.21.The left ren were collected at postnatal 3 day(P 3d),P 7d,P 14d and P 21d of two groups,for detecting HGF protein express in kidney by immunohistochemical method.Results:①The result of HGF expression:HGF protein expressed in each group.The expression increased gradually from P 3d in group Air with the day age prolonged(F=8.85,p＜0.01),but decreased significantly at P 21d(group Air,3d 90.09±6.57,7d 95.55±2.78,14d 98.51±4.81,21d 89.90±3.30).In group HO,HGF protein expression increased gradually from P 3d with the day age prolonged(F=31.49, p＜0.01),with a peak at P 14d,but decreased at P 21d.Compared with group Air,renal HGF protein expression in group HO increased significantly at P 3d,P 7d and P 14d,whose average value were higher than corresponding group Air(p＜0.01).But there was no significant difference at P 21d.②There was a significant positive correlation between renal HGF protein express and cell apoptosis(r=0.464, p＜0.05).Conclusion:HGF protein expression increasing is relevant to the process of renal injury of neonatal rats model with hyperoxia-induced lung injury,which possible related to its restrain on cell apoptosis.