大环内酯类抗生素对早产鼠高氧肺损伤谷胱甘肽和白细胞介素-1β表达的影响

Effects of macrolide antibiotics on the level of glutathione hormone and interleukin-1β after hyperoxia-induced lung injury in premature rats

目的探讨大环内酯类抗生素对高氧肺损伤的干预机制。方法早产SD大鼠生后1天随机分为空气+生理盐水组、空气+红霉素组、高氧+生理盐水组和高氧+红霉素组。高氧组持续暴露于常压氧舱中,氧浓度>85%;空气组置于同一室常压空气中,红霉素组生后1天开始向尾静脉内注射红霉素50mg/kg,每天1次;生理盐水组注射生理盐水0.15ml/kg。各组分别于高氧或空气暴露后1、7、14天提取肺组织标本。采用石蜡包埋切片行HE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肺组织匀浆谷胱甘肽(GSH)和白细胞介素-1β(IL-1β)的水平,二喹啉甲酸法(BCA)检测GSH浓度。结果 (1)与空气+生理盐水组相比,高氧+生理盐水组早产鼠1、7天肺组织中GSH表达水平(ng/ml)显著增高,14天明显降低[1天:(8.9±2.1)比(4.1±0.7),7天:(10.7±0.7)比(4.9±0.9),14天:(4.4±0.7)比(5.3±4.1),P<0.05];高氧+红霉素组1、7、14天GSH表达水平均显著高于高氧+生理盐水组[1天:(9.9±2.0)比(8.9±2.1),7天:(12.2±2.5)比(10.7±0.7),14天(8.4±5.6)比(4.4±0.7),P<0.05]。(2)与空气+生理盐水组相比,高氧+生理盐水组早产鼠7天肺组织中IL-1β表达水平(ng/ml)显著增强,14天明显减弱[7天:(26.4±2.1)比(24.3±2.3),14天:(22.7±2.7)比(27.3±8.2),P<0.05];高氧+红霉素组1、7、14天IL-1β表达水平均显著低于高氧+生理盐水组[1天:(23.0±2.1)比(24.7±2.4),7天:(23.5±1.6)比(26.4±2.1),14天:(21.6±1.3)比(22.7±2.7),P<0.05]。结论红霉素可能通过提高GSH的活性,抑制氧化暴发诱导的炎症介质IL-1β释放,在减轻高氧肺损伤过程中发挥一定抗氧化作用。

Objective To study the effect of macrolide antibiotics （erythromycin） on hyperoxia- induced lung injury in premature rats. Methods One-day-old SD rats （P1） were randomly assigned into four groups： A air （21% 02） ± sodium Chloride group, B air ± erythromycin group, C hyperoxia ± sodium chloride group, D hyperoxia ± erythromycin group. Hyperoxia groups were continuously exposed to high concentration oxygen （oxygen concentration 〉 0. 85）and air group exposed to room air （21% 02 ）. After 1,7,14 days of exposure, all the rats were sacrificed, and the whole lung were isolated. The histological changes were studied using hematoxylin-eosin （HE） staining. GSH and IL-1β in pulmonary tissue homogenate were detected by double antibody sandwich enzyme linked immunosorbent assay （ELISA）. Bicinchoninic acid （BCA） was used to detect GSH protein in lung tissue homogenate. Results （1） Comparing with group A, GSH expression （ng/ml） in group C were significantly increased （P 〈0. 05） after 1,7 days of exposure, then became significantly weak after 14 days of exposure [ day 1 ： （ 8.9 ± 2. 1 ） vs. （4. 1 ± 0. 7 ）, day 7 ： （ 10.7 ± 0. 7 ） vs. （4. 9 ± 0. 9 ）, day 14 ： （4. 4 ± 0. 7） vs. （5.3 ± 4. 1 ）, P 〈 0. 05 ） ]. Comparing with group C, GSH expression in group D were significantly increased after 1,7 and 14 days of exposure （ng/ml） [ day 1 ： （9.9 ± 2.0） vs. （ 8.9 ± 2. 1 ）, day7：（12.2±2.5）vs. （10.7 ±0.7）, day 14：（8.4±5.6）vs. （4.4 ±0.7）, P〈0.05）]. （2） Comparing with group A, IL-113 expression in group C were significantly increased （ P 〈 0. 05 ） after 7 days of exposure, then significantly weaker after 14 days [ 7 day ： （26. 4 ± 2. 1 ） vs. （24. 3 ± 2.3 ）, 14 day ： （22.7 ± 2.7 ） vs. （27.3 ± 8.2, P 〈 0. 05 ） ]. Comparing with group C, IL-113 expression （ng/ml） in group D became significantly weak after 1, 7, 14 days of exposure [ 1 day： （24. 7 ±2.4） vs. （23.0 ±2.1）, 7 day： （26.4 ±2.1） vs. （23.5 ±1.6）, 14 day： （22.7 ±2.7） vs. （21.6±1.3）, P〈 0. 05 ） ]. Conclusions Erythromycin may increase the activity of GSH and reduce the hyperoxia-induced release of inflammatory mediator IL-1β, exerting antioxidation effect to alleviate hyperoxia-induced lung injury in premature rats.