T0901317对急性肺损伤大鼠肺组织LXRα表达的影响及其抗炎作用  

Protective Effects of Liver X receptor-α Activator T0901317 on Rats with Acute Lung Injury

作　　者：徐静[1] 肖波[1] 何春琳[2] 王建春[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 [2]汉中市人民医院,陕西汉中723000

出　　处：《中国呼吸与危重监护杂志》2011年第3期247-251,共5页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：国家自然科学基金资助项目(编号:30570808)

摘　　要：目的探讨肝脏X受体α(LXRα)激活剂T0901317对脂多糖(LPS)所致急性肺损伤(ALI)大鼠动物模型的保护效应。方法 72只雄性Wistar大鼠,按随机数字表法分为对照组、LPS组和T0901317干预组。观察各组大鼠PaO2、肺组织髓过氧化物酶(MPO)活性及肺组织病理变化;采用逆转录-聚合酶链反应(RT-PCR)检测肺组织中LXRα、肿瘤坏死因子α(TNF-α)mRNA表达;采用酶联免疫吸附法(ELISA)检测TNF-α蛋白变化;采用免疫组化染色观察肺组织LXRα蛋白变化。结果与对照组比较,LPS致伤后各时间点PaO2显著降低,肺组织干/湿重比值(W/D)、MPO活性均显著升高(P<0.05),组织病理显示肺组织受损;肺组织LXR-αmRNA表达下降,TNF-αmRNA升高(P<0.05),肺组织匀浆和动脉血清中TNF-α显著升高。免疫组化显示LXRα蛋白在对照组肺组织中表达较高水平,在LPS致伤后可见该蛋白表达较对照组显著下降(P<0.05)。T0901317干预组LXRα在基因和蛋白水平表达上调,TNF-α表达下降,差异均有统计学意义(P<0.05),同时观察到肺部炎症明显减轻。结论在LPS诱发的大鼠ALI模型中,T0901317通过促进LXR-α表达,抑制TNF-α表达,减轻炎性细胞在肺组织的浸润和聚集,从而具有保护作用。Objective To explore the protective effects of liver X receptor-α activator(LXRα) T0901317 on rats with acute lung injury(ALI).Methods Seventy-two male Wistar rats were randomly divided into three goups,ie.a control group,a LPS group,and a T0901317 group.Artery blood gas analysis,lung tissue wet/dry weight ratio,myeloperoxidase activity,and lung histopathological changes were measured.The expressions of LXRα and TNF-α mRNA in lung tissue were detected by RT-PCR.The protein levels of TNF-α and LXRα were examined with ELISA and immunohistochemistry,respectively.Results In the ALI rats,PaO2 decreased,lung W/D weight ratio and myeloperoxidase activity increased significantly compared with the control group(P<0.05).Histopathological examination also revealed obvious lung injury.In the LPS group,the expression of TNF-α mRNA in lung tissue and the level of TNF-α protein in lung homogenate and serum increased markedly(all P<0.05) while the expression of LXR-α mRNA declined significantly(P<0.05).Immunohistochemical staining showed that lung tissues of the normal rats expressed LXRα significantly but in the LPS group the expression of TNF-α and LXR-α in lung tissue decreased markedly(P<0.05).After the treatment with T0901317,the expressions of LXR-α in lung tissues were significantly higher than those in the LPS group both at the mRNA and the protein level(P<0.05).Conclusion T0901317 plays an anti-inflammatory effect through up-regulating the expression of LXR-α and suppressing the expression of TNF-α,thus reduces the infiltration and aggregation of inflammatory cells in lung tissue.

关 键 词：急性肺损伤 脂多糖 肝脏X受体α T0901317 

分 类 号：R563[医药卫生—呼吸系统]