大剂量盐酸氨溴索对大鼠肺损伤后Toll样蛋白受体4/核转录因子-κB的作用研究  

Effects of large-dose of Ambroxol hydrochloride on Toll-like receptor 4/Nuclear transcription factor- kappa B expression in rats with lung injury

作　　者：李晓平[1] 张卫东[1] 姜涛[2] 杜洪印[3] 王文辰[2] 任宏[5] 李磊[1] 祖红林[4] 夏彦民 杨波[1] 

机构地区：[1]天津市第一中心医院胸外科,300192 [2]第四军医大学唐都医院胸外科,710038 [3]天津市第一中心医院麻醉科,300192 [4]天津市第一中心医院血管外科,300192 [5]西安交通大学医学院第一附属医院胸外二科,710061

出　　处：《中华老年医学杂志》2016年第6期647-650,共4页Chinese Journal of Geriatrics

基　　金：国家自然科学基金（81070062）,军队“十二五”课题（12MA208）

摘　　要：目的 研究大剂量盐酸氨溴索对大鼠肺缺血再灌注损伤后Toll样蛋白受体4（TLR-4）/核转录因子-κB（nF－κB）表达的影响及可能作用机制。 方法 将健康雄性SD大鼠60只随机分为4组，每组15只：第1组即对照组；第2组即盐酸氨溴索组；第3组即肺缺血再灌注（I/R）组；第4组即I/R＋盐酸氨溴索组。第2、4组造模前给予静脉注射盐酸氨溴索0.75 g/L，第1、3组造模前给予注射与治疗量等容量的生理盐水。观察肺组织病理学改变并评分，检测湿干重比值（W/D）、白介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）、NF-κB，Western blot方法观察大鼠肺组织TLR-4的表达。 结果 与第1组相比，第3组肺泡壁增宽，肺泡腔内可见出血等炎症表现，W/D、炎性因子显著升高，肺组织W/D 、IL-1β、TNF-α、NF-κB和TLR4表达明显升高；与I/R组相比，第4组肺泡腔内出血、水肿等炎症表现减轻，W/D、炎性因子显著降低，肺组织NF-κB及TLR4表达量明显降低。 结论 大剂量盐酸氨溴索通过下调TLR4/NF-κB信号通路发挥对肺缺血再灌注损伤大鼠的保护作用。Objective To investigate the effect of large-dose of Ambroxol hydrochloride on Toll- like receptor 4 （TLR4）/ Nuclear transcription factor- kappa B（NF-~B）expression in rat after lung ischemia-reperfusion injury（LIRI）, and possible mechanisms. Methods 60 healthy SD rats were randomly assigned into four groups （n = 15, each） ： the first group （control group）, the second group （Amhroxol hydrochloride group）, the third group （ischemia-reperfusion group, I/R）, and the fourth group（I/R q- ambroxol hydrochloride group）. The second and fourth groups were injected with Ambroxol hydroehloride 0.75g/1 by intravenous injection. The first and third groups received equal volume of saline. The LIR-induced pathological changes were observed and graded. The wet-to-dry weight ratio, interleukin-1β（IL-1β）, tumor necrosis factor-α （TNF-α）, nuclear transcription factor-κB （NF-κB）were determined. The protein expression of TLR4 in lung tissues was detected by Western blotting. Results Compared with the control group, the I/R group showed that the thickened alveolar wall,alveolar hemorrhage and other inflammatory changes in lung tissues were found,and that the wet-to-dry weight ratio, and expressions of IL-1β, TNF-α, NF-κB and TLR4 were significantly increased. The alveolar hemorrhage, edema and other inflammatory changes in lung tissues werealleviated,and the wet-to-dry weight ratio, the expressions of inflammatory cytokines, NF-κB and TLR4 in lung tissues were significantly decreased in I/R ＋ ambroxol hydrochloride group versus the I/R group,. Conclusions The large-dose of Ambroxol hydrochloride has a protective effect on lung ischemia-reperfusion injury in rat through down-regulating TLR4/NF-κB signaling pathway.

关 键 词：氨溴索 急性肺损伤 TOLL样受体4 NF-κB 

分 类 号：R563[医药卫生—呼吸系统]