雷洛昔芬对大鼠急性肺损伤保护作用的研究

Protective effect of raloxifene on lung function after acute lung injury in rats

目的探讨雷洛昔芬对大鼠急性肺损伤（acute lung injury，Au）的保护作用。方法30只SD雄性大鼠按随字数字表法分为三组：二次打击前用药组（10只）、二次打击中用药组（10只）和对照组（10只）。所有大鼠腹腔注射5mg／kgLPS，并分别于LPS腹腔注射前1h和腹腔注射后14h对二次打击前用药组和二次打击中用药组用雷洛昔芬30mg／kg灌胃，LPS腹腔注射后16h，所有大鼠均用戊巴比妥钠按40mg／kg行腹腔注射麻醉，股动脉插管监测平均动脉压（MAP），气管内滴入pH为1．2，0．5ml／kg盐酸。盐酸滴入前及滴入后30，90min和4h查动脉血气分析，4h后每组中选取5只大鼠行[^18F]FDG microPET胸部扫描，而后取肺组织进行组织病理学观察。结果血气分析显示二次打击中用药组大鼠能显著改善肺的氧合功能，并能使MAP稳定，[^18F]FDG吸收度及肺组织病理评分在对照组分别为9．01±1．58，12．6±0．97，显著高于二次打击中用药组的4．67±1．33（P〈0．01）和8．20±1．23（P〈0．01）。结论雷洛昔芬对大鼠ALI具有明显保护作用；[^18F]FDG microPET能很好地评价ALI时肺内的炎症反应。

Objective To evalhate the protective effect of oral raloxifene on lung function after acute lung injury （ALl） in rats. Methods Thirty male adult Sprague-Dawley rats were used and divided into three groups： LPS raloxifene hydrochloric acid. group before secondary impact （Group A, n = 10 ） , LPS raloxifene hydrochloric acid group after secondary impact （Group B, n = 10） and control group （n = 10）. All the rats were injected intraperitoneally with 5 mg/kg LPS. Raloxifene （30 mg/kg） was orally administered one hour before LPS injection and 14 hours after LPS injection in Groups A and B. The control group remained free. All the animals were anesthetized by intraperitoneal injection of pentobarbital sodium at 40 mg/kg and the femoral artery was cannulated 16 hours after LPS injection to measure the mean arterial pressure （MAP）. All the rats received a direct intratrachcal injection of hydrochloric acid （ pH = 1.2, 0.5 ml/kg）. Before injection of hydrochloric acid and at 0.5,1.5 and 4 hours after injection of hydrochloric acid, the blood gas was measured. Fifteen rats （five from each group） underwent a micro positron emission tomography （ [ ^18F] FDG microPET） scan of the thorax four hours after hydrochloric acid instillation. Then, the lung tissue was collected for histopathologieal examination. Results The Group B showed better pulmonary gas exchange and more stable MAP compared to the control group. The [ ^18 F ] fluorodeoxyglucose uptake and histological lung injury score were 9.01 ±1.58 and 12.6 ±0.97 respectively in Group B, which were higher than 4.67 ±1.33 and 9.01 ±1.58 respectively in control group （P 〈 0.01 ）. Conclusions Raloxifene exerts significant protective effect on lung function after ALI. [^18F] FDG microPET is a useful method to evaluate the inflammatory reaction during ALI.