PURPOSE High concentrations of oxygen administered to newborn infants with respiratory failure increases oxidant stress and leads to lung injury, characterized by decreased alveolar and capillary development. Cathelicidin belongs to an important group of human antimicrobial peptides that exhibit antioxidant activity; its overexpression reduces hyperoxia-induced oxidative stress. This study evaluated the therapeutic effects of cathelicidin in hyperoxia-induced lung injury in newborn rats. METHODS AND MATERIALS Sprague Dawley rat pups were reared in either room air (RA) or hyperoxia (85% O2) and then randomly treated with low-dose (4 mg/kg) and high-dose (8 mg/kg) cathelicidin in 0.05 mL of normal saline (NS) administered intraperitoneally on postnatal days 1-6. The following six groups were obtained: RA + NS, RA + low-dose cathelicidin, RA + high-dose cathelicidin, O2 + NS, O2 + low-dose cathelicidin, and O2 + high-dose cathelicidin. Lungs were harvested for Western blot and histological analyses on postnatal day 7. RESULTS Compared with the RA-reared rats, the hyperoxia-reared rats exhibited significantly lower body weights, higher mean linear intercept (MLI), lung injury score, interleukin-6, and oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression but lower superoxide dismutase 1 (SOD1) and vascular endothelial growth factor (VEGF) protein expression and vascular density. Cathelicidin treatment attenuated hyperoxia-induced lung injury as demonstrated by lower MLI and injury score and higher VEGF expression and vascular density. CONCLUSIONS Cathelicidin attenuated hyperoxia-induced lung injury and caused a decrease in 8-OHdG and SOD1 protein expression, most likely by inhibiting oxidative stress in the lung.

中文翻译：

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Cathelicidin 通过抑制新生大鼠的氧化应激减轻高氧诱导的肺损伤。

目的 给呼吸衰竭的新生儿提供高浓度的氧气会增加氧化应激并导致肺损伤，其特征是肺泡和毛细血管发育下降。Cathelicidin 属于具有抗氧化活性的一组重要的人类抗菌肽；它的过表达减少了高氧诱导的氧化应激。本研究评估了导管素对新生大鼠高氧性肺损伤的治疗效果。方法和材料 Sprague Dawley 大鼠幼崽在室内空气 (RA) 或高氧 (85% O2) 中饲养，然后用 0.05 的低剂量 (4 mg/kg) 和高剂量 (8 mg/kg) 导管素随机处理出生后第 1-6 天腹腔注射生理盐水 (NS) 毫升。获得以下六组：RA+NS、RA+低剂量导管素、RA + 高剂量导管素、O2 + NS、O2 + 低剂量导管素和 O2 + 高剂量导管素。在出生后第 7 天收集肺进行蛋白质印迹和组织学分析。 结果 与 RA 饲养的大鼠相比，高氧饲养的大鼠表现出显着较低的体重、较高的平均线性截距 (MLI)、肺损伤评分、白细胞介素 6、和氧化应激标记物 8-羟基-2'-脱氧鸟苷 (8-OHdG) 表达，但降低超氧化物歧化酶 1 (SOD1) 和血管内皮生长因子 (VEGF) 蛋白表达和血管密度。导管素治疗减轻了高氧诱导的肺损伤，如较低的 MLI 和损伤评分以及较高的 VEGF 表达和血管密度所证明。结论 Cathelicidin 可减轻高氧诱导的肺损伤并导致 8-OHdG 和 SOD1 蛋白表达降低，