摘要
目的评价伊马替尼对内毒素血症急性肺损伤小鼠的影响。方法采用随机数字表法将60只8~12周龄的SPF级雄性C57BL/6小鼠分为4组(n=15):对照组(C组)、伊马替尼组(I组)、内毒素血症组(LPS组)和伊马替尼+内毒素血症组(I+LPS组)。复制内毒素血症急性肺损伤小鼠模型,24 h后处死小鼠,观察小鼠肺组织病理学检测结果并进行肺损伤评分,测量肺组织湿/干比;ELISA法检测血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(IL-6)的表达;试剂盒检测肺组织丙二醛(malondialdehyde,MDA)、谷胱甘肽(glutathione,GSH)、过氧化氢酶(catalase,CAT)、超氧化物歧化酶(superoxide dismutase,SOD)和还原型谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)水平;Western blot法分析肺组织核转录因子κB(NF-κB)的磷酸化水平、核转录因子红系2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)及血红素氧合酶1(heme oxygenase-1,HO-1)的表达水平。结果与C组相比较,LPS组的肺湿/干比比值[(3.47±0.41)vs.(5.58±0.47)]及肺损伤评分[(1.25±0.89)vs.(10.25±1.75)]升高(P<0.05),血清中TNF-α和IL-6水平上调(P<0.05),SOD、CAT、GSH、GSH/GSSG水平降低(P<0.05),MDA水平增加,p-NF-κB、Nrf2和HO-1蛋白表达上调(均P<0.05);与LPS组比较,I+LPS组肺W/D比值[(5.58±0.47)vs.(4.62±0.38)]及肺损伤评分[(10.25±1.75)vs.(7.00±1.31)]下降(P<0.05),血清TNF-α和IL-6水平下降(P<0.05),SOD、CAT、GSH、GSH/GSSG水平升高(P<0.05),MDA水平下调(P<0.05),p-NF-κB蛋白表达下降,Nrf2和HO-1蛋白表达升高(P<0.05)。结论伊马替尼可改善脓毒症急性肺损伤,其机制可能与抑制氧化应激有关。
Objective To evaluate the effect of imatinib on the endotoxemia-induced acute lung injury in mice.Methods Sixty SPF male,8-12 weeks,C57BL/6 mice were randomly(random)divided into 4 groups(n=15 each):control group(group C),imatinib group(groupⅠ),endotoxemia group(group LPS)and imatinib+endotoxemia group(group I+LPS).The endotoxemia model of acute lung injury was established.After 24 hours,the mice were sacrificed.The pathological changes of lung tissues were evaluated,the lung injury scores were calculated,and the wet/dry ratios of lung tissues were measured.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in serum.Detection kits were used to analyze the levels of malondialdehyde(MDA),glutathione(GSH),catalase(CAT),superoxide dismutase(SOD)and the ratio of reduced glutathione to oxidized glutathione(GSH/GSSG)in lung tissues;The expression levels of phosphorylated nuclear factor-kappa B(p-NF-κB),nuclear factor-erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in lung tissues were analyzed by western blotting.Results Compared with the group C,the wet/dry(W/D)ratio of lungs[(3.47±0.41)vs.(5.58±0.47)],lung injury scores[(1.25±0.89)vs.(10.25±1.75)],and the levels of TNF-αand IL-6 in serum increased in the group LPS(P<0.05).The levels of SOD,CAT,GSH and GSH/GSSG decreased,the level of MDA increased,and the expression of p-NF-κB,Nrf2 and HO-1 protein up-regulated(P<0.05).Compared with the LPS group,the W/D ratio of lungs[(5.58±0.47)vs.(4.62±0.38)]and lung injury scores[(10.25±1.75)vs.(7.00±1.31)]in the I+LPS group decreased(P<0.05),and the levels of TNF-αand IL-6 in the serum decreased(P<0.05).In lung tissues,the levels of SOD,CAT,GSH and GSH/GSSG increased(all P<0.05),the level of MDA decreased(all P<0.05),the expression of p-NF-κB protein decreased,and the expression of Nrf2 and HO-1 protein increased(P<0.05).Conclusions Imatinib improves sepsisinduced acute lung injury in mice,and the mechanism of actions behind may be related to the inhibition of oxidative stress.
作者
李端阳
刘雅茹
周芷晴
杨红
宗晓龙
李真玉
Li Duanyang;Liu Yaru;Zhou Zhiqing;Yang Hong;Zong Xiaolong;Li Zhenyu(Department of Emergency Medicine,The Second Hospital of Tianjin Medical University,Tianjin 300211;Department of Pharmacology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070;Department of Clinical Laboratory,The Second Hospital of Tianjin Medical University,Tianjin 300211)
出处
《中华急诊医学杂志》
CAS
CSCD
北大核心
2024年第8期1104-1109,共6页
Chinese Journal of Emergency Medicine
基金
国家临床重点专科急诊医学科建设项目(2023283)
天津市高层次人才选拔培养工程"青年医学新锐"人才项目[2018(19)]
天津市卫健委中医中西医结合科研课题(2021207)。
