ABSTRACT
Objective To explore the expression of nuclear factor-erythroid 2-related factor 2(Nrf2) and the molecular chaperone of cytoplasmic Keap1 in premature newborn rats exposed to hyperoxia.Methods Completely randomized design method was performed,one-day old preterm SD rats were randomly divided into two groups:hyperoxia group and air group.The preterm SD rats in hyperoxia group were continuously exposed to oxygen(oxygen >0.85)and air group in room air.After 1 ,4,7,10,14 days of exposure,the pre-term SD rats of two groups were sacrificed,whole lung of these rats were isolated,the lung histological chan-ges were observed by HE staining.Total lung RNA was extracted,Nrf2 and Keap1 mRNA were detected by RT-PCR.Western-blot was used to detect the changes of Nrf2 protein expression.Results (1 )Compaired with air group,the expression of Nrf2 in lung tissue of hyperoxia group significantly increased after 4,7 days of exposure(4 d:0.314 ±0.064 vs.0.521 ±0.086,7 d:0.440 ±0.121 vs.0.658 ±0.076)(P 0.05),but had a tendency of decreasing after 7 days.On day 10, 14,its expression in hyperoxia group became significantly weak compared with that of air group(10 d:1.325 ±0.464 vs.0.755 ±0.348,14 d:1.662 ±0.474 vs.0.867 ±0.1 15 )(P <0.05 ).Conclusion Oxidation outbreak results in the abnormal expression of Nrf2 and Keap1 in the lung of premature SD rats induced by hyperoxia exposure,which adjusts the levels of oxidative stress in the body,these changes participate in the development of hyperoxia induced lung injury,the activity of Nrf2 may be increased by hyperoxia exposure, and alleviate hyperoxia lung injury in premature rats through antioxidation of Nrf2.
ABSTRACT
Objectives To explore the effect of erythromycin on glutathione hormone (GSH) and γ-glutamyl cysteine synthetase (γ-GCS) in premature newborn rats exposed to hyperoxia, to study the intervention effect of erythromycin on hype-roxia-induced lung injury. Methods One-day old preterm SD rats were randomly divided into four groups:control group, eryth-romycin group, hyperoxia group, erythromycin+hyperoxia group. Hyperoxia group and hyperoxia+erythromycin group were continuously exposed to oxygen (oxygen concentration>0.85), control group and erythromycin group were in room air. Via cau-dal vein, the preterm rats was injected with erythromycin in erythromycin group and hyperoxia+erythromycin group, sodium chloride in control group and hyperoxia group daily. After 1,7,14 day(s) of hyperoxia (or air ) exposure, the preterm SD rats of four groups were killed, whole lung of these rats were isolated and histological changes were observed by hematoxylin-eosin (HE) staining, GSH andγ-GCS of pulmonary tissue homogenate were detected by double antibody sandwich enzyme linked im-munosorbent assay. Total lung RNA was extracted andγ-GCS mRNA was detected by reverse transcription polymerase chain re-action. Results The results showed that:After 1 and 7 day(s) of exposure, the expression of GSH、γ-GCS andγ-GCS mRNA in four groups showed significant differences(P<0.05). Among them, GSH expression in erythromycin + hyperoxia group was higher than that in the other three groups in 1,7,14 day(s) of exposure with significant differences (P<0.05);GSH expression in erythromycin+hyperoxia group and hyperoxia group reached the peak after 7 days of exposure. The expression ofγ-GCS andγ-GCS mRNA in erythromycin+hyperoxia group and hyperoxia group were higher than the other two groups after 1and 7 day(s) of exposure, the expression ofγ-GCS mRNA in erythromycin+hyperoxia group were higher than that of hyperoxia group with significant differences (P<0.05). Conclusions The expressions of GSH andγ-GCS in the lung of premature SD rats were abnor-mal by oxidation outbreak. Erythromycin may increase the activity ofγ-GCS, improve the anti-oxidation ability of GSH, and al-leviate hyperoxia mediated lung injury in premature rats.