目的：观察红霉素对高氧暴露下早产新生大鼠肺组织中的谷胱甘肽（GSH）和γ-谷氨酰半胱氨酸合成酶（γ-GCS）表达的影响，探讨红霉素对高氧肺损伤的干预作用。方法将孕第21天剖宫产生后1 d的新生SD大鼠随机分为4组：对照组、红霉素组、高氧组、红霉素高氧组。高氧组和红霉素高氧组持续暴露于常压氧舱中，对照组和红霉素组置于同一室常压空气中；红霉素组和红霉素高氧组每天尾静脉注射红霉素，高氧组和对照组注射生理盐水。四组分别于高氧暴露后第1、7、14天取肺组织标本，石蜡包埋切片行苏木精-伊红染色观察肺组织病理学变化，双抗体夹心酶联免疫吸附法分析GSH和γ-GCS的蛋白水平，半定量逆转录聚合酶链反应测定γ-GCS mRNA表达。结果高氧暴露后第1和7天，对照组、红霉素组、高氧组、红霉素高氧组四组间大鼠肺组织GSH、γ-GCS及γ-GCS mRNA表达的差异均有统计学意义（P<0.05）。其中，高氧组和红霉素高氧组的GSH、γ-GCS表达以及红霉素高氧组的γ-GCS mRNA表达均高于对照组和红霉素组，差异有统计学意义（P均<0.05）。第14天，四组间大鼠肺组织GSH、γ-GCS表达的差异无统计学意义（P均>0.05），而红霉素高氧组γ-GCS mRNA表达高于其余三组，差异有统计学意义（P<0.05）。结论氧化爆发能导致GSH与γ-GCS的表达异常。红霉素可能通过上调γ-GCS活性，提高GSH抗氧化，在减轻高氧肺损伤过程中发挥一定抗氧化作用。%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.
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