大剂量盐酸氨溴索对大鼠肺缺血再灌注损伤后的肺保护机制  

Protective effect of large dose of ambroxol hydrochloride on lung ischemia-reperfusion injury in rats

作　　者：杨波[1] 张卫东[1] 李小飞[2] 王荣[3] 李建忠[4] 李晓平[1] 李明江[1] 杜洪印[5] 姜涛[2] 

机构地区：[1]天津市第一中心医院胸外科,天津300192 [2]第四军医大学唐都医院胸外科,陕西西安710038 [3]西安交通大学航天航空学院,陕西西安710049 [4]哈尔滨医科大学附属第二医院心血管外科,黑龙江哈尔滨150001 [5]天津市第一中心医院麻醉科,天津300192

出　　处：《西安交通大学学报（医学版）》2016年第3期367-371,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81070062);军队"十二五"课题(12MA208)~~

摘　　要：目的探讨大剂量盐酸氨溴索对大鼠肺缺血再灌注损伤后肺的保护作用以及可能的作用机制。方法将健康雄性SD大鼠60只随机分成4组:对照组、氨溴索组、肺缺血再灌注(I/R)组、I/R+氨溴索组,每组15只。造模前分别给予大剂量氨溴索组和I/R+氨溴索组静脉注射盐酸氨溴索0.75g/L,分别给予对照组和I/R组注射与上述氨溴索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)、细胞凋亡数目、核转录因子-κB(NF-κB),Western blot方法观察大鼠肺组织Toll样蛋白4(Toll-like receptor 4,TLR4)信号通路的蛋白表达水平。结果与对照组相比,I/R组肺泡壁增宽,肺泡腔内可见出血等炎症表现,W/D、炎症因子显著升高,肺组织W/D、IL-1β、TNF-α、凋亡细胞、NF-κB活性和TLR4信号通路相关蛋白表达水平明显升高;与(I/R)组相比,I/R+氨溴索组肺泡腔内出血、水肿等炎症表现减轻,W/D、炎症因子、凋亡细胞显著降低,肺组织NF-κB转录活性及TLR4信号通路表达水平明显降低。结论大剂量盐酸氨溴索通过下调TLR4信号通路发挥对缺血再灌注损伤大鼠的肺保护作用。Objective To observe the effects of large-dose ambroxol hydrochloride on lung ischemia- reperfusion injury （LIRI） and discuss the protection of ambroxol hydrochloride on Toll-like receptor 4 （TLR4）/ nuclear transcription factor-kappa B （NF-xB） after lung ischemia-reperfusion injury in rats. Methods We randomly assigned 60 healthy SD rats into four groups （n = 15 for each）., control group, ambroxol hydrochloride group （0.75 g/L）, ischemia-reperfusion group （I/R）, and I/R＋ ambroxol hydrochloride group. The ambroxol hydrochloride group and I/R＋ambroxol hydrochloride group were injected large dose of ambroxol hydrochloride by intravenous injection. The control group and the I/R group received normal saline. The effects of ambroxol hydrochloride on lung ischemia-reperfusion （LIR）-induced pathological changes and inflammatory cytokines release level were examined. DNA ends situ labelinz assay （TUNEL） was used to detect the apoptosis of cells. NF-xBp65 was detected by immunohistochemistry. In addition, the TLR4 signaling pathway activation in lung tissues was detected by Western blot analysis. Results Compared with those in the control group, some hemorrhage and inflammation changes of lung tissues were observed; the W/D ratio, inflammatory cytokines, apoptosis of cells, NF- ~Bp65 and TLR4 signaling pathway protein expression in I/R group was obviously increased. Compared with I/R group, some mild hemorrhage and inflammation changes of lung tissues were observed; W/D ratio, inflammatory cytokines, apoptosis of cells, NF-xBp65 activity, and TLR4 signaling pathway expression were all decreased significantly in I/R ＋ ambroxol hydrochloride group. Oonclusion Large dose of ambroxol hydrochloride can protect rats with lung ischemia-reperfusion injury by downregulating TLR4 signaling pathway.

关 键 词：大剂量盐酸氨溴索 肺缺血再灌注损伤 肺保护 Toll样蛋白受体4(TLR4) 

分 类 号：R655.3[医药卫生—外科学]