J Korean Med Sci.  2007 Dec;22(6):1042-1047. 10.3346/jkms.2007.22.6.1042.

Erythropoietin Attenuates Hyperoxia-Induced Lung Injury by Down-modulating Inflammation in Neonatal Rats

• Lee JH
• Sung DK
• Koo SH
• Shin BK
• Hong YS
• Son CS
• Lee JW
• Chang YS
• Park WS

• KMID: 1785767
• DOI: http://doi.org/10.3346/jkms.2007.22.6.1042

Abstract

This study was done to determine whether recombinant human erythropoietin (rhEPO) treatment could attenuate hyperoxia-induced lung injury, and if so, whether this protective effect is mediated by the down-modulation of inflammation in neonatal rats. Newborn Sprague Dawley rat pups were subjected to 14 days of hyperoxia (>95% oxygen) within 10 hr after birth. Treatment with rhEPO significantly attenuated the mortality and reduced body weight gain caused by hyperoxia. With rhEPO treatment, given 3 unit/gm intraperitoneally at 4th, 5th, and 6th postnatal day, hyperoxia- induced alterations in lung pathology such as decreased radial alveolar count, increased mean linear intercept, and fibrosis were significantly improved, and the inflammatory changes such as myeloperoxidase activity and tumor necrosis factor-alpha expression were also significantly attenuated. In summary, rhEPO treatment significantly attenuated hyperoxia-induced lung injury by down-modulating the inflammatory responses in neonatal rats.

Keyword

Erythropoietin; Bronchopulmonary Dysplasia; Inflammation; Animals, Newborn

MeSH Terms

Animals
Animals, Newborn
*Cytoprotection
Disease Models, Animal
Erythropoietin, Recombinant/*therapeutic use
Female
Hyperoxia/*pathology
Inflammation/*drug therapy
Lung/*drug effects/pathology
Peroxidase/metabolism
Rats
Rats, Sprague-Dawley
Survival Rate
Tumor Necrosis Factor-alpha/genetics

Figure

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  Fig. 1 Representative photomicrographs showing Grade 1 (A), Grade 3 (B), Grade 5 (C), and Grade 7 (D) fibrosis, respectively (H&E, magnification, ×40).

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  Fig. 2 Survival rate in each experimental group. NC, Normoxia control group; NE, Normoxia with erythropoietin treatment group; HC, Hyperoxia control group; HE, Hyperoxia with erythropoietin treatment group. *p value <0.05 compared to NC; †p value <0.05 compared to NE; ‡p value <0.05 compared to HC.

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  Fig. 3 Effect of eythropoietin treatment on lung histology after hyperoxia in newborn rats. (H&E, magnification, ×40). (A) Lung structure of neonatal rats in normoxia at d 14 (NC). (B) Erythropoietin treatment has no apparent affect on the lung structure of rats maintained in normoxia (NE). (C) As shown, hypeoxia decreases lung septation and causes lung septation and causes distal air space enlargement (HC). (D) Erythropoietin treatment during hyperoxia increases alveolarization (HE).

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  Fig. 4 Histopathologic analysis in each experimental group. (A) Radial alveolar count (RAC), (B) Mean linear interscept (MLI), (C) Fibrosis score. *p value <0.05 compared to normoxia control group (NC); †p value <0.05 compared to normoxia with EPO group (NE); ‡p value <0.05 compared to hyperoxia control group (HC).

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  Fig. 5 Myeloperoxidase activity (A) and tumor necrosis factor-a expression (B) in each experimental group. *p value <0.05 compared to Normoxia control group (NC); †p value <0.05 compared to Normoxia with EPO group (NE); ‡p value <0.05 compared to hyperoxia control group (HC).

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