Retinoic acid diminished the expression of lung tissue matrix metalloproteinase-2 and matrix metalloproteinase-9 in hyperoxia-exposed premature rats through regulating mitogen-activated protein kinases / 中华儿科杂志
Chinese Journal of Pediatrics
; (12): 347-353, 2008.
Article
de Zh
| WPRIM
| ID: wpr-326146
Bibliothèque responsable:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To further investigate the protective effect of retinoic acid (RA) on hyperoxia induced lung injury and the role of RA as a modulator on mitogen-activated protein kinases (MAPKs).</p><p><b>METHODS</b>Establishment of hyperoxia (85%) induced lung injury model of premature Sprague-Dawley (SD) rats: 21 d gestational age SD rat's fetuses (term = 22 d) were delivered by hysterectomy. Within 12 - 24 h after birth, the premature rat pups were randomly divided into 4 groups: Group I, air-exposed control group; Group II, hyperoxia-exposed group; Group III, air plus RA-exposed group, Group IV, hyperoxia plus RA-exposed group. Group I and III were remained in room air, and group II and IV were placed in 85% oxygen. The pups in Group III and IV were injected with RA (500 microg/kg, every day) intraperitoneally. The entire lung tissues of premature rat pups were collected at 4 d, 7 d and 14 d. The mRNA levels of MMP-2 and MMP-9 were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). MMP-2 and MMP-9 activities were measured by zymography. Western blot was used to detect phosphorylated and total nonphosphorylated form of ERKs, JNKs and p38.</p><p><b>RESULTS</b>Exposure to oxygen for 4 d, 7 d, and 14 d resulted in increased mRNA levels of MMP-2 and MMP-9 compared with air-exposed control group (P < 0.01 for all). The mean protein levels of active MMP-2 and pro/active MMP-9 after exposure to O2 were higher than air control groups on each experimental day (P < 0.01 or < 0.05). The phosphorylated ERK1/2, JNK1/2 and p38 proteins in hyperoxia-exposed group increased markedly compared with air-exposed control group (P < 0.01 for all). The pups treated with RA in the hyperoxic environment expressed significantly lower mRNA levels of MMP-2 and MMP-9 than the hyperoxic control pups on each experimental day (P < 0.05 for all). The levels of active MMP-2 and pro/active MMP-9 decreased to a different degree after RA treatment in hyperoxia exposure rat pups. In addition, RA treatment led to a decrease of p-JNK1/2 and p-38 (P < 0.01 for all) protein levels and a further elevation of p-ERK1/2 compared with hyperoxia-exposed group.</p><p><b>CONCLUSION</b>Hyperoxia exposure elevated the expression of MMP-2 and MMP-9 markedly, which played a role in oxygen-induced lung injury. RA could have a protective effect on hyperoxia induced lung injury by decreasing active levels of JNK and p38, which subsequently reduce the expression and activation of MMP-2 and MMP-9.</p>
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Pharmacologie
/
Trétinoïne
/
Rat Sprague-Dawley
/
Hyperoxie
/
Matrix metalloproteinase 2
/
Matrix metalloproteinase 9
/
Mitogen-Activated Protein Kinases
/
Modèles animaux de maladie humaine
/
Lésion pulmonaire
/
Poumon
Limites du sujet:
Animals
langue:
Zh
Texte intégral:
Chinese Journal of Pediatrics
Année:
2008
Type:
Article