目的：探讨PPAR-γ配体罗格列酮在新生大鼠高氧肺损伤中的保护作用。方法：取新生Sprague-Dawley大鼠96只，随机分为对照组、高氧组和罗格列酮治疗组。对照组在空气中饲养，后两组暴露在85%～90%氧气中。治疗组给予罗格列酮腹腔内注射每日1次（2 mg/kg）。3组于实验第1、3、7、14 d各处死8只大鼠并取其肺组织，行苏木精-伊红染色观察其病理形态改变，同时取其肺泡灌洗液（BALF），检测其中的丙二醛（MDA）含量及白细胞计数。结果：对照组在各时间点均未见明显病理性改变；高氧组3 d时肺泡上皮细胞肿胀，肺泡腔内可见大量炎性渗出液，14 d时肺泡减少，肺间质增厚，肺泡发育受阻；与高氧组相比，罗格列酮治疗组炎症反应表现较轻，肺泡发育障碍有所缓解。与对照组相比，高氧组3 d时辐射状肺泡计数(RAC)明显下降（P<0.05），MDA和白细胞计数明显增高（P<0.05），这种变化一直持续至14 d（P<0.05）；与高氧组相比，罗格列酮治疗组3、7、14 d各亚组RAC明显增高（P<0.05），MDA和白细胞计数水平较低（P<0.05）。结论：高氧肺损伤时出现肺部的急性炎症反应和肺泡发育受阻，罗格列酮对高氧肺损伤可能具有保护作用。
Abstract
OBJECTIVE: To study the protective effects of PPAR gamma ligand rosiglitazone (RGZ) against hyperoxia-induced lung injury in neonatal rats. METHODS: Ninety-six neonatal Sprague-Dawley (SD) rats were randomly divided into three groups: control (room air exposure), hyperoxia (85%-90% oxygen exposure) and RGZ treatment［85%-90% oxygen exposure plus RGZ solution injection (2 mg/kg, once daily)］. Rats were sacrificed at 1, 3, 7 and 14 days after exposure. Hematoxylin and eosin staining was used to evaluate histological changes in lung tissues. The contents of malondialdehyde (MDA) and leucocyte count in bronchoalveolar lavage fluid (BALF) were measured. RESULTS: No pathological changes were found in the control group at any time point after exposure. Alveolar epithelial cell swelling, interstitial edema and massive infiltration of inflammatory cells were found in the hyperoxia group 3 days after exposure. At 14 days after exposure, the number of pulmonary alveoli was reduced, alveolus interstitium had thickened and organizational structure had become disordered in the hyperoxia group. The RGZ treatment alleviated significantly the hyperoxia induced alterations in lung pathology. Radial alveoli count (RAC) decreased significantly in the hyperoxia group compared with the control group from 3 days through to 14 days after exposure (P<0.05). The RGZ treatment group showed significantly increased RAC compared with the hyperoxia group at 3, 7 and 14 days after exposure (P<0.05). MDA content and leucocyte count in BALF increased significantly in the hyperoxia group 3 days after exposure (P<0.05), reached a peak 7 days after exposure (P<0.01) and remained higher 14 days after exposure (P<0.05) compared with the control group. The RGZ treatment group significantly decreased MDA content and leucocyte count compared with the hyperoxia group (P<0.05). CONCLUSIONS: Hyperoxia may cause acute and chronic pulmonary injuries in neonatal rats, characterized by acute inflammatory reactions and decreased alveolus in lungs. RGZ may have protective effects against hyperoxia induced lung injury.
关键词
高氧肺损伤 /
过氧化物酶体增殖物活化受体&gamma /
罗格列酮 /
丙二醛 /
新生大鼠
Key words
Hyperoxic lung injury /
Peroxisome proliferators-activated receptor-&gamma /
Rosiglitazone /
Malondialdehyde /
Neonatal rats
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