Keratinocyte growth factor-2 intratracheal instillation significantly attenuates ventilator-induced lung injury in rats.
Keratinocyte growth factor-2 intratracheal instillation significantly attenuates ventilator-induced lung injury in rats.
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DOI：
10.1111/jcmm.12269
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发表时间：
2014-06
影响因子：
5.3
通讯作者：
She J
中科院分区：
文献类型：
--
作者：
Bi J;Tong L;Zhu X;Yang D;Bai C;Song Y;She J
保存或恢复正常肺泡上皮屏障功能对肺水肿的消退至关重要。角化细胞生长因子-2 （KGF-2）是一种有效的上皮细胞有丝分裂原，可能在预防呼吸机诱导的肺损伤（VILI）中起作用，这种损伤经常发生在机械通气患者中。本研究的目的是测试KGF-2在大鼠VILI中的作用。选取健康成年雄性spraguedawley大鼠40只，随机分为4组，HVZP组（高容积零呼气末正压）和HVZP+KGF-2组大鼠分别在4 h HVZP通气（20 ml/kg）前72 h气管内给予等量PBS和5 mg/kg KGF-2，对照组和KGF-2组同样给予PBS和KGF-2，仅行气管切开并自主呼吸。检测支气管肺泡灌洗液中炎性因子（肿瘤坏死因子-α、巨噬细胞炎性蛋白2）、中性粒细胞和总蛋白水平及肺组织中表面活性剂蛋白mRNA表达；观察肺泡ⅱ型细胞数量、肺含水量及肺形态。结果表明，与单独使用HVZP相比，KGF-2预处理可显著改善肺水肿和炎症，并增加表面活性剂蛋白mRNA和肺泡II型细胞。我们的结果表明，KGF-2可能被认为是预防人类VILI或其他急性肺损伤疾病的有希望的方法。
Preservation or restoration of normal alveolar epithelial barrier function is crucial for pulmonary oedema resolution. Keratinocyte growth factor-2 (KGF-2), a potent epithelial cell mitogen, may have a role in preventing ventilator-induced lung injury (VILI), which occurs frequently in mechanically ventilated patients. The aim of the study was to test the role of KGF-2 in VILI in rats. Forty healthy adult male Sprague-Dawley rats were randomly allocated into four groups, where rats in Groups HVZP (high-volume zero positive end-expiratory pressure) and HVZP+KGF-2 were given intratracheally equal PBS and 5 mg/kg KGF-2 72 hrs before 4 hrs HVZP ventilation (20 ml/kg), respectively, while PBS and KGF-2 were administered in the same manner in Groups Control and KGF-2, which underwent tracheotomy only with spontaneous breathing. Inflammatory cytokines (tumour necrosis factor-α, macrophage inflammatory protein 2), neutrophil and total protein levels in bronchoalveolar lavage fluid and surfactant protein mRNA expression in lung tissue were detected; the number of alveolar type II cells, lung water content and lung morphology were also evaluated. The results indicate that pre-treatment with KGF-2 showed dramatic improvement in lung oedema and inflammation compared with HVZP alone, together with increased surfactant protein mRNA and alveolar type II cells. Our results suggest that KGF-2 might be considered a promising prevention for human VILI or other acute lung injury diseases.