TLR4/NF-κB信号通路在胸部撞击和胸部撞击-失血性休克复苏致大鼠急性肺损伤中作用的比较  

Comparison of roles of Toll-like receptor 4/NF-κB signal pathway in acute lung injury induced by blunt chest trauma and by blunt chest trauma-hemorrhagic shock and resuscitation in rats

作　　者：吴晓静[1] 段薇娜[1] 薛锐[1] 夏中元[1] 赵博[1] 

机构地区：[1]武汉大学人民医院麻醉科,430060

出　　处：《中华麻醉学杂志》2014年第2期233-236,共4页Chinese Journal of Anesthesiology

摘　　要：目的 比较Toll样受体4（TLR-4）/NF-κB信号通路在胸部撞击和胸部撞击-失血性休克复苏“双重打击”致大鼠急性肺损伤中的作用.方法 SPF级健康雄性SD大鼠40只,8周龄,体重240 ～ 280 g,采用随机数字表法,将大鼠分为3组（n=10）：假手术组（S组）、胸部撞击组（T组）和胸部撞击-失血性休克复苏组（THSR组）.将砝码（300 g）于95 cm高处自由落体,撞击大鼠心前区以制备胸部撞击模型,5 min后经股动脉缓慢放血,15 min内使MAP降至35 ～ 45 mmHg并维持此水平60 min,随后进行复苏,以制备“双重打击”模型.于模型制备后6h时,取动脉血样进行血气分析,计算氧合指数（PaO2/FiO2）,测定血清TNF-α浓度.取血后处死大鼠,取肺组织,观察病理学结果,采用免疫组化法和Western blot法测定肺组织TLR4表达和NF-κB活性.结果 与S组比较,T组和THSR组PaO2和PaO2/FiO2降低,PaCO2和血清TNF-α浓度升高,肺组织TLR4表达上调,NF-κB活性增强（P＜0.05）;与T比较,THSR组PaO2和PaO2/FiO2降低,PaCO2和血清TNF-α浓度升高,肺组织TLR4表达上调,NF-κB活性增强（P＜ 0.05）;THS组肺组织病理学损伤程度较T组明显加重.结论 与在胸部撞击致大鼠急性肺损伤中的作用比较,TLR4/NF-κB信号通路在胸部撞击-失血性休克复苏“双重打击”致大鼠急性肺损伤中的作用明显增强.Objective To compare the roles of Toll-like receptor 4 （TLR4）/NF-κB signal pathway in acute lung injury （ALl） induced by blunt chest trauma and by blunt chest trauma-hemorrhagic shock and resuscitation （double hits） in rats.Methods Forty male Sprague-Dawley rats,aged 8 weeks,weighing 240-280 g,were randomly assigned into 3 equal groups （n =10 each） using a random number table：sham operation group （S group）,blunt chest trauma group （T group）,and blunt chest trauma and hemorrhagic shock and resuscitation group （group THSR）.Lung contusion was induced in anesthetized rats by dropping a 300 g weight onto a precordial protective shield to direct the impact force away from the heart and toward the lungs.Blood was withdrawn via the femoral artery 5 min later until MAP was decreased to 35-45 mmHg within 15 min and maintained at this level for 60 min,followed by resuscitation.At 6 h after the model was established,the arterial blood samples were collected for blood gas analysis and detection of tumor necrosis factor-alpha （TNF-α） concentrations in serum.Oxygenation index （PaO2/FiO2） was calculated.The rats were then sacrificed and pulmonary specimens were obtained for determination of TLR4 expression and NF-κB ac tivity （by immunohistochemistry and Western blot） in lung tissues and for microscopic examination.Results Compared with group S,PaO2 and PaO2/FiO2 were significantly decreased,PaCO2 and TNF-α concentrations in serum were increased,TLR4 expression was up-regulated,and NF-κB activity was enhanced in T and THSR groups （P 〈 0.05）.Compared with group T,PaO2 and PaO2/FiO2 were significantly decreased,PaCO2 and TNF-α concentrations in serum were increased,TLR4 expression was up-regulated,and NF-κcB activity was enhanced in THSR group （P 〈 0.05）.The histopathological damage to lung tissues was aggravated in THSR group as compared with T group.Conclusion The role of TLR-4/NF-κB signal pathway in ALI induced by blunt chest traumahemorrhagic shock and resuscitatio

关 键 词：胸部损伤 休克 出血性 呼吸窘迫综合征 成人 TOLL样受体4 NF-ΚB 

分 类 号：R459.7[医药卫生—急诊医学]