大鼠严重胸部创伤肺泡巨噬细胞TLR4的表达及意义.docVIP

大鼠严重胸部创伤肺泡巨噬细胞TLR4的表达及意义 作者：张伟，蒋耀光，吕凤林，胡承香，李磊 【关键词】 胸部创伤 　　摘要： 目的 观察大鼠严重胸部创伤后肺泡巨噬细胞TLR4基因及蛋白表达水平的变化，并探讨其意义。方法 建立大鼠严重胸部创伤模型，支气管肺泡灌洗分离、培养肺泡巨噬细胞，利用Western、Northern分子生物学技术检测创伤前、创伤后2、4、8、16、24小时肺泡巨噬细胞TLR4的表达水平。结果 利用小型多功能生物撞击机，以400kPa驱动压力对大鼠右侧上胸壁进行致伤，可建立稳定可靠并符合临床特点的严重胸部创伤动物模型；严重胸部创伤可上调TLR4在肺泡巨噬细胞内的表达，表达高峰在伤后8小时，伤后24小时恢复正常。结论 TLR4的上调参与了创伤后失控性炎症反应的病理生理过程。本研究为创伤性急性肺损伤的发病机制提供了一定的实验及理论依据。 　　关键词：胸部创伤；肺泡巨噬细胞；Toll样受体4；内毒素；肺损伤；大鼠 　　Change of Tolllike receptor 4 expression on alveolar macrophages in severe thoracic trauma in rats 　　ZHANG Wei,JIANG Yaoguang,LV Fengling,et al. 　　(Thoracic and Cardiovascular，Surgery Research Center,Institute of Surgery Research,Daping Hospital,Third Military Medical University,Chongqing 400042,China) 　　Abstract： Objective To observe the changes of alveolar macrophages on TLR4mRNA and expression of TLR4 protein.Methods Models of severe thoracic trauma were established,alveolar macrophages were obtained by collecting bronchoalveolar lavage fluid,and then separated and cultured.TLR4mRNA and the expression of TLR4 protein were measured by northern and western blot before and 2,4,8,16,24h after trauma.Results A stable and reliable severe thoracic trauma model was successfully established with 400kPastrike on the upperright part of chest of the rat by a multiplefunction strike apparatus.The expression of TLR4 could be upregulated after trauma,and the highest expression of alveolar macrophages occurred 8,24h after injury.Conclusion The upregulation of TLR4 participated in the pathological procedure of excessive inflammation.The present study presented the valuable laboratoy and theoretical evidence for the research of ALI caused by severe thoracic trauma. 　　Key words:thoracic trauma;alveolar macrophages;TollLike Receptor 4;LPS;lung injury；rats 严重胸部创伤常并发创伤性急性肺损伤(acute lung injury，ALI)，并极易发展为急性呼吸窘迫综合征（ARDS）。尽管对ARDS的研究已有30余年，但ARDS死亡率仍较高，其发病机制仍不清楚。对其发病机制的探讨是当今创伤研究领域的热点之一，也是临床工作中迫切需要解决的课题。有关研究表明，严重胸部创伤能引起机体