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Pulmonary Collagen Content in 1‐Year‐Old Rats Exposed to Postnatal Hyperoxia
Author(s) -
Sobotik Atzie,
Pegelow David,
Goss Kara,
Haraldsdottir Kristin,
Braun Rudolf,
Barton Greg,
Tetri Laura,
Eldridge Marlowe
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1298.3
Subject(s) - hyperoxia , bronchopulmonary dysplasia , hydroxyproline , lung , extracellular matrix , medicine , physiology , pathology , pathological , andrology , endocrinology , biology , pregnancy , gestational age , biochemistry , genetics
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants exposed to oxygen therapy postnatally. Although it is a vital, life‐saving treatment, oxygen therapy is closely associated with long‐term consequences, including decreased alveolarization and reductions in pulmonary vasculature cross‐sectional area. Previous studies using a BPD rodent model have demonstrated an increase in lung collagen content within the first 20 days of birth. This suggests that the aberrant lung development in the BPD animal model is associated with pathological changes in the extracellular matrix (ECM) (i.e. increased collagen content). No study to our knowledge has looked at collagen accumulation later in life as a result of early postnatal hyperoxia treatment. Furthermore, it is currently unknown whether or not there are sex differences in the ECM remodeling. The purpose of this study is to determine if 14 days of postnatal hyperoxia exposure affects collagen accumulation in the lungs of 1‐year‐old male and female rats. Methods An established rat model of BPD using Sprague‐Dawley rats was. Within 12 hours of birth, rats were placed in a hyperoxic (HYP, 85% O 2 ) chamber, or normoxic (NORM, 21% O 2 ) chamber. After 14 days in respective conditions, all rats were allowed to age until 1 year in room air. The aged rats were sacrificed, and tissues were harvested and flash‐frozen in liquid nitrogen. Colorimetric assays were performed on lung tissue to assess overall hydroxyproline content as a measurement of collagen. Histology was also analyzed to visually assess collagen levels using Masson's trichrome‐stained lung slides. Four pictures were taken per slide, each picture was divided into 9 sections, and a blinded party scored each segment's collagen content on a scale of 1–3 (0=none, 1=mild, 2=moderate, 3=severe). Two‐way ANOVAs were used to determine the effects of sex, HYP exposure, and their influence on lung collagen. Results The colorimetric assay revealed that aged hyperoxic females (n=7) demonstrate a 23% increase in collagen content compared to aged normoxic females (n=5, p=0.02). Aged HYP males (n=6) demonstrated similar pulmonary collagen content compared to aged normoxic males (n=3) based on colorimetric assay. However, histopathologic examination revealed increased collagen deposition in both males and female aged HYP rats (p=0.07, n=2–3). Conclusions These results suggest that females exposed to HYP in early‐postnatal life are more susceptible to collagen accumulation in the lungs, which may be indicative of increased lung injury as compared to males. Support or Funding Information NIH‐NHLBI R01 – HL115061 NIH‐NHLBI R01 Supplement – HL1150613