CXCR4 blockade attenuates hyperoxia-induced lung injury in neonatal rats.
CXCR4 blockade attenuates hyperoxia-induced lung injury in neonatal rats.
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作者：
Drummond S;Ramachandran S;Torres E;Huang J;Hehre D;Suguihara C;Young KC
肺部炎症是支气管肺发育不良(BPD)发病机制中的关键因素。基质衍生因子-1(SDF-1)及其受体趋化因子受体4(CXCR4)调节炎症反应。目前尚不清楚CXCR4拮抗剂是否能减轻新生儿高氧性肺损伤的肺部炎症反应。目的：探讨CXCR4拮抗剂是否能减轻实验性BPD大鼠的肺损伤。新生大鼠从出生后第2天(P2)-P16开始暴露于常氧(RA)或高氧(FiO2=0.9)，从P5到P15随机接受CXCR4拮抗剂AMD3100或安慰剂(PL)。在P16时对肺泡化、血管生成和炎症进行评估。与RA相比，高氧性肺损伤组肺泡形成减少，肺血管密度降低，肺部炎症加重。相比之下，用AMD3100治疗的高氧幼鼠改善了肺泡化，增加了血管生成。肺结构的改善伴随着支气管肺泡灌洗液、巨噬细胞和中性粒细胞计数的减少，以及肺髓过氧化物酶活性的降低。CXCR4拮抗剂可减轻实验性BPD新生大鼠的肺部炎症反应，改善肺泡和血管结构。这些发现提示了一种新的治疗策略来减轻早产儿BPD的肺损伤。
Lung inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Stromal derived factor-1 (SDF-1) and its receptor chemokine receptor 4 (CXCR4) modulate the inflammatory response. Whether antagonism of CXCR4 will alleviate lung inflammation in neonatal hyperoxia-induced lung injury is unknown. To determine whether CXCR4 antagonism would attenuate lung injury in rodents with experimental BPD by decreasing pulmonary inflammation. Newborn rats exposed to normoxia (RA) or hyperoxia (FiO2=0.9) from postnatal day 2 (P2)-P16 were randomized to receive the CXCR4 antagonist, AMD3100 or placebo (PL) from P5 to P15. Lung alveolarization, angiogenesis, and inflammation were evaluated at P16. As compared to RA, hyperoxic-PL pups had a decrease in alveolarization, reduced lung vascular density and increased lung inflammation. In contrast, AMD3100-treated hyperoxic pups had improved alveolarization and increased angiogenesis. This improvement in lung structure was accompanied by a decrease in bronchoalveolar lavage fluid macrophage and neutrophil count and reduced lung myeloperoxidase activity. CXCR4 antagonism decreases lung inflammation and improves alveolar as well as vascular structure in neonatal rats with experimental BPD. These findings suggest a novel therapeutic strategy to alleviate lung injury in preterm infants with BPD.
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影响因子：
20.1
作者：
Young KC;Torres E;Hatzistergos KE;Hehre D;Suguihara C;Hare JM
通讯作者：
Hare JM
影响因子：
2.5
作者：
Philip, Alistair G. S.
通讯作者：
Philip, Alistair G. S.
影响因子：
45.3
作者：
Devine, SM;Flomenberg, N;DiPersio, JF
通讯作者：
DiPersio, JF
DOI：
10.1165/rcmb.2012-0383oc
发表时间：
2013-05-01
影响因子：
6.4
作者：
Hummler, Stefanie C.;Rong, Min;Wu, Shu
通讯作者：
Wu, Shu
影响因子：
2.7
作者：
McGrath, KE;Koniski, AD;Palis, J
通讯作者：
Palis, J