急性肺损伤大鼠肺组织肝脏X受体α表达的研究  

Study on expression of liver X receptor-α in rat lung tissue in acute lung injury

作　　者：徐静[1] 王建春[1] 肖波[1] 王关嵩[1] 

机构地区：[1]第三军医大学新桥医院全军呼吸内科研究所,重庆400037

出　　处：《中国危重病急救医学》2009年第4期203-206,I0001,共5页Chinese Critical Care Medicine

基　　金：国家自然科学基金项目（30570808）

摘　　要：目的观察内毒素性急性肺损伤（ALI）大鼠肝脏X受体α（LXRα）的改变，探讨LXRα在ALI发病中的作用机制。方法将48只Wistar大鼠随机均分为两组。采用尾静脉注射脂多糖（LPS）5mg／kg复制大鼠ALI模型，对照组静脉注射生理盐水2．5ml／kg。于致伤后1、2、4和8h取大鼠动脉血进行血气分析及肿瘤坏死因子-α（TNF-α）水平检测；取肺测定肺湿／干重（W／D）比值、髓过氧化物酶（MPO）活性及肺组织病理学改变；用逆转录-聚合酶链反应（RT-PCR）检测肺组织LXRα mRNA、TNF-α mRNA表达；用酶联免疫吸附法（ELISA）检测TNF-α含量变化；用免疫组化法观察肺组织LXRα蛋白表达情况。结果与对照组比较，ALI组致伤后各时间点动脉血氧分压（PaO2）均显著降低，肺W／D比值、MPO活性均显著升高（P均〈0．05）；病理观察显示肺组织受损；肺组织LXRα mRNA表达下降。TNF-α mRNA表达升高（P均〈0．05），肺组织匀浆和动脉血清中TNF-α亦显著升高，4h达高峰。免疫组化显示对照组肺组织表达较高水平LXRα蛋白，ALI组在LPS致伤后可见LXRα蛋白表达较对照组显著下降（P均〈0．05）。结论正常大鼠肺组织可表达LXRα，LPS可引起ALI大鼠肺组织LXRα的基因和蛋白表达下降，这可能与ALI发病有关。Objective To observe changes in liver X receptor-α （LXRα） in acute lung injury （ALl） in rats induced by lipopolysaccharide （LPS） to explore mechanism of LXRα in pathogenesis of ALI. Methods Forty-eight Wistar rats were randomly divided into two groups. ALl model was reproduced by intravenous injection of LPS （5 mg/kg）, and control group was injected with normal saline （2.5 ml/kg）. At 1, 2, 4, 8 hours after ALl, artery blood gas analysis, lung tissue wet/dry weight （W/D） ratio, myeloperoxidase （MPO） activity, lung histopathologic changes were observed. The expressions of LXRa and tumor necrosis factor-α （TNF-α） mRNA were detected by reverse transcription-polymerase chain reaction （RT-PCR）. TNF-α content was measured with enzyme linked immunosorbent assay （ELISA）. LXRa protein in lung tissues was assessed by immunohistochemistry. Results Compared with the control group, in ALI rats at different time points, partial pressure of oxygen in arterial blood （PaO2） decreased significantly, lung W/D weight ratio and MPO activity increased significantly （all P〈（0.05）, histopathology of lung revealed signs of injury. After injury, expression of LXRa mRNA in lung tissue decreased markedly, and expression of TNF a mRNA in lung tissue increased markedly （all P〈0. 05）. TNF-α increased markedly in lung homogenate and blood serum at the same period, and TNF-α reached peak value at 4 hours. Immunohistochemical staining of LXRa showed that lung tissues of normal rats express LXRα significantly, however, after injury, expression of LXRα in lung tissue decreased markedly （all P〈0.05）. Conclusion Lung tissues of normal rats express LXRα. The decreased LXRα mRNA and protein expressions in the lung tissue of rats with ALl caused by LPS may be associated with the occurrence of ALI.

关 键 词：肝脏X受体α 急性肺损伤 脂多糖 大鼠 

分 类 号：R686[医药卫生—骨科学]