Toll样受体4改善脓毒症致小鼠急性肺损伤的机制  

Mechanism of Toll-like receptor 4 improves the sepsis-induced acute lung injury in mice

作　　者：金丽[1] 廖文杰 徐建如[1] 葛志华[1] 邵峰[1] 李晗 崔晓晖 刘亚琴[1] Jin Li;Liao Wenjie;Xu Jianru;Ge Zhihua;Shao Feng;Li Han;Cui Xiaohui;Liu Yaqin(Emergency Department,the Third People's Hospital of Nantong City,Nantong 226000,China;Department of Emergency Medicine,the Second People's Hospital of Lianyungang,Lianyungang 222006,China)

机构地区：[1]南通市第三人民医院急诊科,江苏南通226000 [2]连云港市第二人民医院急诊内科,江苏连云港222006

出　　处：《国际免疫学杂志》2021年第5期500-506,共7页International Journal of Immunology

基　　金：南通市卫生健康委员会科研立项课题(QA2019036)。

摘　　要：目的分析Toll样受体4(Toll-like receptor 4,TLR4)改善脓毒症致小鼠急性肺损伤(acute lung injury,ALI)的机制。方法将45只小鼠分为三组:对照组(C组),脓毒病组(S组)和预处理组(P组),每组15只。S组的小鼠腹膜内注射10 mg/kg脂多糖(lipopolysaccharide,LPS),P组在注射LPS之前1 h,先注射了TLR4 mAb(5μg/g),C组小鼠腹膜内注射等质量的生理盐水。分别在6、12和24 h检测三组肺组织中TLR4的mRNA表达水平,肿瘤坏死因子(tumor Necrosis Factor,TNF)-α和白细胞介素(interleukin,IL)-6的血清表达水平及小鼠肺中的水分含量和肺部病理形态学变化。结果在6 h时,三组小鼠肺组织中水含量变化的组间差异无统计学意义(P>0.05),而在12、24 h时,S组小鼠肺组织中的水含量较C组和P组明显升高,组间差异具有统计学意义[12 h:(84.85±5.32)mg比(71.27±3.50)mg比(78.32±4.10)mg,24 h:(87.23±5.28)mg比(71.83±3.14)mg比(81.12±3.56)mg,F值分别为12.062和17.892,P值均<0.05]。在6、12、24 h时,S组小鼠血清中TNF-α表达水明显高于C组和P组,组间差异均有统计学意义[6 h:(259.43±18.47)pg/mL比(29.24±5.12)pg/mL比(155.35±13.26)pg/mL,12 h:(185.58±14.21)pg/mL比(33.31±3.46)pg/mL比(114.52±13.21)pg/mL,24 h:(115.26±16.65)pg/mL比(34.75±4.25)pg/mL比(81.45±10.44)pg/mL,F值分别为366.930,224.191和60.645,P值均<0.05]。随着LPS处理时间的增加,S组与P组小鼠血清中TNF-α表达水平明显降低(F值分别为285.123和134.257,P值均<0.05)。在6、12、24 h时,S组小鼠血清中IL-6表达水平较C组和P组明显升高,组间差异均有统计学意义[6 h:(234.41±24.65)pg/mL比(84.36±5.56)pg/mL比(157.26±17.43)pg/mL,12 h:(300.58±23.78)pg/mL比(86.23±7.23)pg/mL比(204.64±15.37)pg/mL,24 h:(395.16±15.36)pg/mL比(84.75±9.25)pg/mL比(308.35±14.88)pg/mL,F值分别为89.621,202.495和708.632,P值均<0.05]。随着LPS处理时间的增加,S组与P组小鼠血清中IL-6水平明显升高(F值分别为208.460和352.900,P值均<0.05)。在6、12、24 h�Objective To analyze the mechanism of Toll-like receptor 4(TLR4)in improving acute lung injury(ALI)in mice caused by sepsis.Methods Total of 45 mice were divided into three groups:control group(group C),sepsis group(group S)and pretreatment group(group P),with 15 mice in each group.Mice in group S were injected with 10 mg/kg lipopolysaccharide(LPS)intraperitoneally,and in group P were injected with TLR4 mAb(5μg/g)1 h before LPS injection,in group C were injected intraperitoneally with physiological saline of equal quality.The expression levels of TLR4 mRNA,tumor necrosis factor(TNF)-α,interleukin(IL)-6,and the water content and pathological changes in three groups of lung tissues were detected at 6,12,and 24 h respectively.Results At 6 h,there was no significant difference in the change of water content in the lung tissue of mice among the three groups(P>0.05),while at 12 and 24 h,the water content in the lung tissue of group S was significantly higher than that of group C and group P[12 h:(84.85±5.32)mg vs(71.27±3.50)mg vs(78.32±4.10)mg,24 h:(87.23±5.28)mg vs(71.83±3.14)mg vs(81.12±3.56)mg,F values were 12.062 and 17.892 respectively,both P values<0.05].At 6,12,and 24 h,the expression level of serum TNF-α in group S was significantly higher than that of group C and group P[6 h:(259.43±18.47)pg/mL vs(29.24±5.12)pg/mL vs(155.35±13.26)pg/mL,12 h:(185.58±14.21)pg/mL vs(33.31±3.46)pg/mL vs(114.52±13.21)pg/mL,24 h:(115.26±16.65)pg/mL vs(34.75±4.25)pg/mL vs(81.45±10.44)pg/mL,F values were 366.930,224.191 and 60.645 respectively,all P values<0.05].With the increase of LPS treatment time,the expression levels of serum TNF-α in group S and group P mice were significantly reduced(F values were 285.123 and 134.257 respectively,both P values<0.05).At 6,12,and 24 h,the expression level of serum IL-6 in group S was significantly higher than that in group C and group P[6 h:(234.41±24.65)pg/mL vs(84.36±5.56)pg/mL vs(157.26±17.43)pg/mL,12 h:(300.58±23.78)pg/mL vs (86.23±7.23)pg/mL vs(204.64±15.37)pg/mL,24

关 键 词：脓毒症 急性肺损伤 TOLL样受体4 炎性因子 机制 

分 类 号：R459.7[医药卫生—急诊医学]