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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 investigate the intervention mechanism of macrolide antibiotics on hyperoxic lung injury. Methods One-day preterm SD rats were randomly divided into air + saline group, air + erythromycin group, hyperoxia + saline group and hyperoxia + erythromycin group. Oxygen concentration> 85%. The air group was placed in the same room air at normal pressure. Erythromycin 50 mg / kg was injected into the tail vein one day after erythromycin group, 1 times a day; normal saline group injected saline 0.15ml / kg. Lung tissue samples were collected from the rats at 1, 7, 14 days after exposure to hyperoxia or air exposure, respectively. Paraffin-embedded sections were used to observe the pathological changes of lung tissue. The levels of glutathione (GSH) and interleukin-1β (IL-1β) in lung homogenate were analyzed by double antibody sandwich enzyme-linked immunosorbent assay. Quinolinecarboxylic acid method (BCA) for the determination of GSH concentration. Results (1) Compared with air + saline group, the expression level of GSH (ng / ml) in lung tissue of hypoxia + saline group increased significantly on day 1,7 and decreased significantly on day 14 [day 1 (4.1 ± 0.7), 7 days: (10.7 ± 0.7) vs (4.9 ± 0.9), 14 days: (4.4 ± 0.7) vs (5.3 ± 4.1), P < The levels of GSH in groups 1, 7 and 14 were significantly higher than that in hyperoxia + saline group [1 day: (9.9 ± 2.0) vs (8.9 ± 2.1), 7 days: (12.2 ± 2.5) vs (10.7 ± 0.7) , 14 days (8.4 ± 5.6) vs (4.4 ± 0.7), P <0.05]. (2) Compared with the air + saline group, the expression of IL-1βin the lung tissue in the hyperoxia + saline group increased significantly (ng / ml) on day 7 and significantly decreased on the 14th day [7 days: (26.4 ± 2.1 ) (24.3 ± 2.3), 14 days (22.7 ± 2.7) vs (27.3 ± 8.2), P <0.05]. The levels of IL-1β in high oxygen and erythromycin groups were significantly lower than those in the high oxygen and erythromycin groups (23.5 +/- 1.6) vs (26.4 +/- 2.1), 14 days: (21.6 +/- 1.3) vs (22.7 +/- 2.7 ), P <0.05]. Conclusion Erythromycin may inhibit the release of IL-1β, an inflammatory mediator induced by oxidative outburst, and may play a role in reducing oxidative damage during hyperoxia-induced lung injury by increasing GSH activity.