重组人促红细胞生成素对新生大鼠高体积分数氧肺损伤的防治效果

Interferon Effects of Recombinant Human Erythropoietin on Hyperoxic Lung Injury in Neonatal Rats

目的探讨重组人促红细胞生成素(rhEPO)对新生大鼠高体积分数氧(高氧)肺损伤的防治作用。方法新生SD大鼠96只随机分为:空气加9 g/L盐水组(Ⅰ组),空气加rhEPO组(Ⅱ组),高氧加9 g/L盐水组(Ⅲ组),高氧加rhEPO组(Ⅳ组)。Ⅲ、Ⅳ组新生大鼠暴露于950 mL/L氧气中,Ⅱ、Ⅳ组新生大鼠于暴露第2、4、6天予rhEPO800 U/kg腹部皮下注射。在暴露第3、7、14天,各组分别取8只处死,HE染色观察其肺组织结构变化,双抗体夹心法测定其肺组织IL-8。Western blot检测其核因子-κB(NF-κB)p65蛋白水平。结果与Ⅰ组比较,随高氧暴露时间延长,Ⅲ组第3天出现肺泡炎性反应渗出,第7天更为明显,第14天肺泡数量减少,大小不均,肺大泡形成;Ⅳ组病理改变减轻,炎性反应细胞浸润减少。Ⅳ组第7、14天肺组织核因子-κB(NF-κB)p65水平较Ⅲ组显著减少[(0.28±0.07)%vs(0.35±0.07)%,(0.27±0.05)%vs(0.33±0.06)%Pa<0.05],其肺组织匀浆中IL-8水平较Ⅲ组有所减少[(112.38±32.08)ng/Lvs(158.0±37.33)ng/L,(98.78±29.66)ng/Lvs(170.88±42.26)ng/L Pa<0.05]。结论rhEPO对新生大鼠高氧肺损伤有保护作用,机制可能与抑制NF-κB活化、减少IL-8分泌有关。

Objective To explore the interferon effects of recombinant human erythropoietin （rhEPO） on hyperoxic lung damage of neonatal rats. Methods Neonatal SD rats were randomly divided into 4 groups ： air - exposed and saline group （ group Ⅰ ） , air - exposed rhEPO - treated group （ group Ⅱ ）, hyperoxia - exposed and saline group （ group Ⅲ ）, hyperoxia - exposed rhEPO - treated group （ group Ⅳ ）. The rats in Group Ⅲ and Ⅳ were exposed to 950 mL/L oxygen,rats in group Ⅱ and Ⅳ were received rhEPO（800 U/kg） on postnatal day 2,4 and 6. At day 3,7,14 after exposed, the lungs were removed, 8 cases of rats of each group were used to assess lung histologic changes by HE staining, IL - 8 of lung tissues and nuclear factor - κB （ NF -κB） p65 protein levels were detected by Western blot. Results Compared with group Ⅰ , in group Ⅲ, inflammatory cell infiltration was found at day 3, inflammatory cell infiltration was enhanced at day 7, alveolar septa were widen and the number of alveoli decreased, and normal alveolarization disappeared with fibrosis forming at day 14. With rhEPO treatment, hyeroxia - induced alterations in lung pathology were significantly improved, and compared with group Ⅲ, in group Ⅳ, NF-κBp65 proteinlevels decreased[（0.28±0.07）% vs（0.35±0.07）%,（0.27±0.05）% vs（0.33±0.06）% P,〈0.05 ], IL-8 expression were also significantly attenuated [ （ 112.38 ± 32.08 ） ng/L vs （ 158.0 ± 37.33 ） ng/L, （ 98.78 ± 29.66） ng/L vs （ 170. 88 ± 42.26） ng/L P, 〈 0. 05 ]. Conclusions rhEPO has a protective effect on hyperoxia lung injury, it may be related to decrease levels of NF - κB and IL - 8 in the lungs. Treatment of preterm infants with rhEPO might reduce the risk of developing BPD.