红霉素对高氧暴露早产鼠肺组织肿瘤坏死因子-α和白细胞介素-8的干预作用

Intervention effect of erythromycin on tumor necrosis factor-α and interleukin-8 in hyperoxia-induced lung tissue of premature newborn rats

目的 观察大环内酯类抗生素红霉素对高氧暴露下早产新生大鼠肺组织肿瘤坏死因子（tumor necrosis factor,TNF）-α和白细胞介素（interleukin,IL）-8表达的影响,探讨红霉素对高氧肺损伤的干预作用.方法 早产新生SD大鼠生后ld按随机数字表法随机分为4组：空气暴露＋生理盐水组、空气暴露＋红霉素组、高氧暴露＋生理盐水组及高氧暴露＋红霉素组.空气暴露组置于同一室常压空气中;高氧暴露组持续暴露于常压氧舱中,氧浓度＞85％.4组早产鼠分别于空气或高浓度氧暴露后1、7、14d提取肺组织标本.采用石蜡包埋切片行苏木精-伊红染色观察肺组织的病理学变化.采取ELISA法分析血清细胞因子TNF-α和IL-8的水平.结果 （1）与空气暴露＋生理盐水组比较,高氧暴露1、7d,高氧暴露＋生理盐水组早产鼠肺组织TNF-α和IL-8表达水平显著增强[1 d：TNF-α：（16.163±0.574） ng/ml vs.（21.923±2.066） ng/ml,IL-8：（18.214±3.649） ng/ml vs.（23.546±5.240） ng/ml;7 d：TNF-α：（15.940±0.821） ng/ml vs.（19.688±0.764） ng/ml,IL-8：（18.541±4.114） ng/ml vs.（24.255±4.692） ng/ml],尤其TNF-α表达增强出现更早,14 d明显减弱（P＜0.05）.（2）与高氧暴露＋生理盐水组比较,红霉素干预后l、7、14d,高氧暴露＋红霉素组早产鼠肺组织中TNF-α和IL-8表达水平显著降低（P＜0.05）[1 d：TNF-α：（21.923±2.066） ng/ml vs.（18.903±1.851） ng/ml,7 d：IL-8：（24.255±4.692） ng/ml vs.（23.508±3.543） ng/ml,14 d：TNF-α：（16.443±5.466） ng/ml vs.（14.453±0.963） ng/ml],但相对于1、7d时,14d降低程度轻.结论 氧化爆发诱导的炎症介质TNF-α和IL-8释放参与高氧肺损伤的发生发展过程,红霉素可能通过机体免疫调节作用,抑制炎症介质释放,在减轻高氧肺损伤过程中发挥重要作用.

Objective To explore the effect of macrolide antibiotics（erythromycin） on tumor necrosis factor（TNF）-α and interleukin（IL）-8 in hyperoxia-induced lung tissue of premature newborn rats,and to study the intervention effect of erythromycin on hyperoxia-induced lung injury.Methods One-day old preterm Sprague Dawley rats were randomly divided into four groups by random number table method：air ＋ sodium chloride group,air ＋ erythromycin group,hyperoxia ＋ sodium chloride group,hyperoxia ＋ erythromycin group.Hyperoxia groups were continuously exposed to oxygen （oxygen ＞ 0.85） and air group in room air.After 1,7,14 days of exposure,the preterm rats of four groups were sacrificed,whole lung of these rats were isolated,the lung histological changes were observed by hematoxylin-eosin staining,TNF-α and IL-8 in pulmonary tissue homogenate were detected by ELISA.Results The results showed that：（1） Compared with air ＋ sodium chloride group,TNF-α and IL-8 expression in hyperoxia ＋ sodium chloride group were significantly increased（P ＜ 0.05） after 1,7 days of exposure [1 d：TNF-α：（16.163 ± 0.574） ng/ml vs.（21.923 ±2.066） ng/ml,IL-8：（18.214 ±3.649） ng/ml vs.（23.546 ± 5.240） ng/ml ;7 d：TNF-α：（15.940 ±0.821） ng/ml vs.（19.688 ±0.764） ng/ml,IL-8：（18.541 ± 4.114） ng/ml vs.（24.255 ±4.692） ng/ml],in particular,TNF-α expression appeared to increase earlier,their expression became significantly weak in 14 days （P ＜ 0.05）.（2） Compared with hyperoxia ＋ sodium chloride group,TNF-α and IL-8 expression in hyperoxia ＋erythromycin group became significantly weak after 1,7,14 days of exposure（P ＜0.05） after the intervention of erythromycin [1 d：TNF-α：（21.923 ± 2.066） ng/ml vs.（18.903 ± 1.851） ng/ml,7 d：IL-8：（24.255 ±4.692） ng/ml vs.（23.508 ±3.543） ng/ml,14 d：TNF-α：（16.443 ±5.466） ng/ml vs.（14.453 ±0.963）ng/ml],but their expression became weaker in 14 days than that in 1,7 days.Conclusion The release of inflammatory mediators TNF-α and IL-8 induced by oxidation outbreak participates in the development of hyperoxia induced lung injury,erythromycin may regulate immune function,inhibits the levels of oxidant-mediated TNF-α and IL-8 induced by oxidation outbreak,and alleviate hyperoxia lung injury in premature rats.