PMID- 19951473
OWN - NLM
STAT- MEDLINE
DCOM- 20110111
LR  - 20160607
IS  - 0578-1310 (Print)
IS  - 0578-1310 (Linking)
VI  - 47
IP  - 6
DP  - 2009 Jun
TI  - [Anti-inflammatory effects of erythropoietin on hyperoxia-induced 
      bronchopulmonary dysplasia in newborn rats].
PG  - 446-51
AB  - OBJECTIVE: Bronchopulmonary dysplasia (BPD) is a multifactorial disease resulting 
      from the impact of injury (including oxygen toxicity, barotrauma, volutrauma, and 
      infection) on the immature lung. Oxygen toxicity is thought to be a major 
      contributing factor in the pathogenesis in BPD. Previous animal studies have 
      shown that exposure to hyperoxia in the neonatal period causes lung structural 
      changes that are similar to the histology seen in human infants with BPD. 
      Erythropoietin (EPO) has pleiotropic actions including antioxidant, 
      anti-apoptotic, anti-inflammatory and angiogenic effects. Animal experiments 
      reveal that EPO may have protective effects on hyperoxic lung injury, but the 
      mechanisms remain unknown. The aim of the study was to evaluate the 
      anti-inflammatory effects and understand mechanism of action of EPO on the 
      hyperoxia-induced BPD in newborn rats. METHOD: Several litters of Wistar pups 
      were pooled together within 12 hours after birth and randomly divided into four 
      groups: I. air-exposed control group, II. air-exposed human recombinant 
      erythropoietin (rhEPO)-treated group, III. hyperoxia-exposed placebo group and 
      IV. hyperoxia-exposed rhEPO-treated group . Group III and IV rats were exposed to 
      85% oxygen. Group II and IV rats received rhEPO (1200 IU/kg) subcutaneously on 
      postnatal days 0 and 2. Group I and III received 0.9% saline in the same way. 
      Pups from each group were sacrificed on days 3, 7, and 14. Blood hemoglobin 
      concentration, hematocrit and platelet count were determined by blood cell 
      analyzer. Total protein content in bronchoalveolar lavage fluid (BALF) and 
      myeloperoxidase (MPO) were measured by biochemical assay. Changes of monocyte 
      chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil 
      chemoattractant-1 (CINC-1) mRNA expressions were measured by RT-PCR. RESULT: In 
      group III, there were a few inflammatory cells infiltrations in interstitium on 
      day 3 and inflammatory response worsened on day 7. Alveolar and capillary 
      hypoplasia and interstitial fibrosis were evident on day 14. The pathological 
      changes were ameliorated greatly in group IV and the survival was prolonged. 
      There were no abnormal raises of hemoglobin concentration, hematocrit and 
      platelet count in group IV compared with group I. Total protein concentration in 
      BALF was measured as a marker for capillary leakage. MPO is a major constituent 
      of neutrophil cytoplasmic granules and its activity therefore is a direct measure 
      of neutrophil presence and an indirect indicator of lung injury. Total protein 
      concentration and MPO in BALF were greatly depressed in group IV compared with 
      group III, P<0.05, P<0.001. The upregulation of genes of CINC-1 and MCP-1 was 
      closely related with lung inflammation caused by oxidative stress. MCP-1 and 
      CINC-1 mRNA expression were detected and it was found that their changes were in 
      line with the degree of lung inflammation. MCP-1 and CINC-1 mRNA expression 
      increased in group III compared with group I especially on day 7, P<0.01 or 
      <0.001. The changes of MCP-1 and CINC-1 mRNA were positively correlated with 
      changes of MPO in BALF covering all groups on days 3, 7 and 14, respectively (r = 
      0.391, P<0.05; r = 0.701, P<0.01; r = 0.600, P<0.01; r = 0.471, P<0.01; r = 
      0.789, P<0.01; r = 0.588, P<0.01). CONCLUSION: EPO could significantly reduce the 
      lung inflammatory cell infiltration, and capillary endothelial cell injury in 
      hyperoxic lung injury in newborn rats. The mechanism may be related with the 
      inhibition of MCP-1 and CINC-1 gene expression by EPO.
FAU - Wang, Xiao-lei
AU  - Wang XL
AD  - Department of Pediatrics, Shengjing Hospital of China Medical University, 
      Shenyang 110004, China.
FAU - Xue, Xin-dong
AU  - Xue XD
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Er Ke Za Zhi
JT  - Zhonghua er ke za zhi = Chinese journal of pediatrics
JID - 0417427
RN  - 0 (Chemokine CCL2)
RN  - 0 (Recombinant Proteins)
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Erythropoietin/*pharmacology
MH  - Female
MH  - Hyperoxia/complications/*pathology
MH  - Lung/drug effects/metabolism/*pathology
MH  - Lung Injury/etiology/*metabolism/pathology
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Recombinant Proteins
EDAT- 2009/12/03 06:00
MHDA- 2011/01/12 06:00
CRDT- 2009/12/03 06:00
PHST- 2009/12/03 06:00 [entrez]
PHST- 2009/12/03 06:00 [pubmed]
PHST- 2011/01/12 06:00 [medline]
PST - ppublish
SO  - Zhonghua Er Ke Za Zhi. 2009 Jun;47(6):446-51.