临床儿科杂志 ›› 2014, Vol. 32 ›› Issue (5): 476-479.

• 实验研究 • 上一篇    下一篇

红霉素对高氧暴露早产鼠肺组织谷胱甘肽与γ-GCS表达的影响

蔡成1, 裘刚1, 龚小慧1, 魏东1, 胡勇1, 赵焕虎2   

  1. 1上海市儿童医院 上海交通大学附属儿童医院新生儿科(上海 200040);2中央民族大学中国少数民族传统医学研究所(北京 100081)
  • 收稿日期:2013-11-22 出版日期:2014-05-15 发布日期:2014-05-15

Effects of erythromycin on glutathione hormone and γ- glutamyl cysteine synthetase in premature newborn rats’ hyperoxia-induced lung injury 

CAI Cheng, QIU Gang, GONG Xiaohui, WEI Dong, HU Yong, ZHAO Huanhu   

  1.  (1 Department of Neonatology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, 200040; 2 Chinese Minority Ethnic Groups Traditional Medicine Research Center of Central University for Nationalities; Beijing 100081, China)
  • Received:2013-11-22 Online:2014-05-15 Published:2014-05-15

摘要:

 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 孕第21天剖宫产的生后1 d新生SD大鼠随机分为四组,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,差异均有统计学意义(P<0.05)。第14天,四组间大鼠肺组织GSH、γ-GCS表达的差异均无统计学意义(P>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。

Abstract:  Objective 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 hyperoxia-induced lung injury. Methods One-day old preterm SD rats were randomly divided into four groups: control group, erythromycin 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 caudal 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 and γ-GCS of pulmonary tissue homogenate were detected by Double antibody sandwich enzyme linked immunosorbent assay. Total lung RNA was extracted and γ-GCS mRNA was detected by reverse transcription polymerase chain reaction. Results The results showed that: After 1 and 7 day(s) of exposure, the expression of GSH、γ-GCS and γ-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 of γ-GCS and γ-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 of γ-GCS mRNA in erythromycin + hyperoxia group were higher than that of hyperoxia group with significant differences (P<0.05). Conclusions The expressions of GSH and γ-GCS in the lung of premature SD rats were abnormal by oxidation outbreak. Erythromycin may increase the activity of γ- GCS, improve the anti-oxidation ability of GSH, and alleviate hyperoxia mediated lung injury in premature rats.