基于MGB1-TLR4-NF-κB信号通路分析右美托咪定对脓毒症小鼠急性肺损伤的保护作用  

Analysis of the protective effect of dexmedetomidine on acute lung injury in septic mice based on MGB1-TLR4-NF-κB signal pathway

作　　者：吴华兵 肖秀英 詹玮玮 隗莉 胥春梅 Wu Huabing;Xiao Xiuying;Zhan Weiwei;Kui Li;Xu Chunmei(Department of Anesthesiology, Sinopharm Gezhouba Central Hospital, Hubei Province,Yichang 443000,China)

机构地区：[1]三峡大学第三临床医学院/国药葛洲坝中心医院麻醉科,湖北宜昌443000

出　　处：《疑难病杂志》2021年第12期1205-1209,共5页Chinese Journal of Difficult and Complicated Cases

基　　金：湖北省科技计划项目(2018CFB354)。

摘　　要：目的探究乳腺球蛋白(MGB1)-Toll样受体4(TLR4)-核因子κB(NF-κB)信号通路在脓毒症小鼠急性肺损伤中的作用机制及右美托咪定的保护作用。方法2017年8—12月于三峡大学第三临床医学院动物实验中心进行实验,将36只BALB/c小鼠按照完全随机法分为空白对照组、模型组及右美托咪定组(Dex组),每组12只。模型组及Dex组采用脂多糖(LPS)构建脓毒症小鼠急性肺损伤模型,Dex组小鼠给予右美托咪定(Dex),空白对照组和模型组小鼠给予等量生理盐水,观察各组小鼠肺组织病理形态结构变化、肺损伤指标[肺组织湿干重比(W/D)、肺损伤评分]及炎性因子[白介素-6(IL-6)、IL-1β、肿瘤坏死因子(TNF-α)、髓过氧化物酶(MPO)]水平。采用Western-blot法检测MGB1-TLR4-NF-κB通路的蛋白表达。结果空白对照组小鼠肺组织染色均匀且清晰可见,结构完整,排列紧密且有序,无明显炎性细胞浸润;模型组肺组织染色较深,边缘模糊,形态结构不完整,排列杂乱,毛细血管内皮细胞受损出血,肺泡空腔内观察到大量炎性细胞浸润;Dex组肺组织较为清晰,结构相对完整,排列较为整齐,较模型组炎性反应程度显著减轻,且无弥漫性出血。与空白对照组比较,模型组小鼠W/D比值、肺损伤评分显著升高(t=14.587、15.013,P均<0.01);与模型组比较,Dex组小鼠上述指标均显著降低(t=12.405、7.696,P均<0.01)。与空白对照组比较,模型组肺组织IL-6、IL-1β、TNF-α和MPO水平显著升高(t=98.601、18.049、33.506、5.929,P均<0.01);与模型组比较,Dex组上述指标水平显著下降(t=50.881、9.054、9.490、4.515,P均<0.01)。与空白对照组比较,模型组肺组织MGB1、TLR4、NF-κB的蛋白表达显著上调(t=24.779、22.033、22.642,P均<0.01);与模型组比较,Dex组上述通路的蛋白表达均显著下调(t=21.394、18.644、17.781,P均<0.01)。结论右美托咪定通过抑制MGB1-TLR4-NF-κB信号通路的活化,可以改善脓毒症小鼠的�Objective To explore the mechanism of signaling pathway of breast globulin(MGB1)toll like receptor 4(TLR4)nuclear factorκB(NF-κB)in acute lung injury in septic mice and protective effect of dexmedetomidine.Methods The experiment was conducted in the animal experiment center of the Third Clinical Medical College of Three Gorges University from August to December 2017.36 BALB/c mice were randomly divided into blank control group,model group and dexmedetomidine group(DEX group),with 12 mice in each group.The acute lung injury model of septic mice was established by lipopolysaccharide(LPS)in model group and DEX group.Dexmedetomidine(DEX)was given to mice in dex group,and the same amount of normal saline was given to mice in blank control group and model group.The pathological morphological changes of lung tissue,lung injury indexes(lung tissue wet dry weight ratio(W/D),lung injury score)and inflammatory factor(interleukin 6)were observed(IL-6),IL-1β,Tumor necrosis factor(TNF-α),Myeloperoxidase(MPO)]level.MGB1-TLR4-NF-κB was detected by Western blot.Results The lung tissue of the blank control group was evenly stained and clearly visible,with complete structure,compact and orderly arrangement,and no obvious inflammatory cell infiltration.In the model group,the lung tissue was stained deeply,the edge was blurred,the morphological structure was incomplete,the arrangement was disordered,the capillary endothelial cells were damaged and bleeding,and a large number of inflammatory cell infiltration was observed in the alveolar cavity.In dex group,the lung tissue was clear,the structure was relatively complete and arranged orderly,the degree of inflammatory reaction was significantly reduced compared with the model group,and there was no diffuse bleeding.Compared with the blank control group,the w/D ratio and lung injury score in the model group were significantly higher(t=14.587,15.013,P<0.01).Compared with the model group,the above indexes in dex group were significantly lower(t=12.405,7.696,P<0.01).Compared with the

关 键 词：脓毒症 急性肺损伤 乳腺球蛋白-Toll样受体4-核因子κB信号通路 右美托咪定 小鼠 

分 类 号：R563[医药卫生—呼吸系统] R631.2[医药卫生—内科学]