摘要
目的 研究高迁移率族蛋白B1(HMGB1)基因敲除减轻脓毒症小鼠急性肺损伤及抑制Toll样受体4(TLR4)/核因子-κB(NF-κB)通路的作用。方法 野生型(WT)小鼠分为WT-Sham组和WT-模型组,HMGB1基因敲除(KO)小鼠分为KO-Sham组和KO-模型组。WT-模型组和KO-模型组采用盲肠结扎穿孔术制备脓毒症ALI模型,WT-Sham组和KO-Sham组进行假手术操作。造模后24 h,检测动脉血氧分压(PaO_(2)),计算氧合指数(OI),检测肺组织病理改变,计算肺损伤评分,检测血清及肺组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6、活性氧簇(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)的浓度,肺组织中HMGB1、TLR4、核NF-κB的表达。结果 WT-模型组的PaO_(2)、OI、血清及肺组织SOD的浓度低于WT-Sham组,肺损伤评分、血清及肺组织中TNF-α、IL-1β、IL-6、ROS、MDA的浓度、肺组织中HMGB1、TLR4、核NF-κB的表达水平高于WT-Sham组(P<0.05);KO-模型组肺组织中不表达HMGB1,PaO_(2)、OI、血清及肺组织SOD的浓度高于WT-模型组,肺损伤评分、血清及肺组织中TNF-α、IL-1β、IL-6、ROS、MDA的浓度、肺组织中TLR4、核NF-κB的表达水平低于WT-模型组(P<0.05)。结论敲除HMGB1减轻脓毒症小鼠ALI,相关的分子机制可能是抑制TLR4/NF-κB通路介导的炎症反应和氧化应激反应。
Objective To study the effect of high mobility group box B1(HMGB1) gene knockout on alleviating acute lung injury and inhibiting toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) pathway of sepsis mice.Methods Wild-type(WT) mice were divided into WT-Sham group and WT-model group,and HMGB1 knockout(KO) mice were divided into KO-sham group and KO-model group.Sepsis ALI model was established by cecal ligation and perforation in WT-model group and KO-model group.Sham operation was performed in WT-Sham group and KO-Sham group.24 h after modeling,the partial pressure of arterial oxygen(PaO_(2)) was detected,oxygenation index(OI) was calculated,pathological changes of lung tissue were detected and lung injury score was calculated,the concentrations of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),in serum and lung tissues and the expression of HMGB1,TLR4 and nuclear NF-κB in lung tissues were detected.Results The PaO_(2),OI and the concentration of SOD in serum and lung tissue of WT-model group were lower than those of WT-Sham group,the lung injury scores,the concentrations of TNF-α,IL-1β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of HMGB1,TLR4 and nuclear NF-κB in lung tissue were higher than those in WT-Sham group(P<0.05).HMGB1 was not expressed in lung tissue of KO-model group,and the concentrations of PaO_(2),OI and the concentration of SOD in serum and lung tissue of KO-model group were higher than those of WT-model group,the lung injury scores,the concentrations of TNF-α,IL-1β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of TLR4 and nuclear NF-κB in lung tissue were lower than those of the WT-model group(P<0.05).Conclusion HMGB1 gene knockout alleviates acute lung injury of sepsis mice,the related molecular mechanism may be the inhibition of TLR4/NF-κB pathway mediated inflammation and oxidative stress.
作者
张志斌
李瑞彤
郑卫伟
林雪容
牛宁宁
王慧
苑萌
韩树池
薛乾隆
Zhang Zhibin;Li Ruitong;Zheng Weiwei;Lin Xuerong;Niu Ningning;Wang Hui;Yuan Meng;Han Shuchi;Xue Qianlong(Dept of Emergency,The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000)
出处
《安徽医科大学学报》
CAS
北大核心
2024年第2期248-253,共6页
Acta Universitatis Medicinalis Anhui
基金
2023年度河北省卫生健康委科研基金项目(编号:20231452)。
