中国临床药理学与治疗学2024,Vol.29Issue(11) :1232-1239.DOI:10.12092/j.issn.1009-2501.2024.11.004

基于TLR4/NF-κB信号通路研究蜂毒肽对急性肺损伤小鼠的作用及机制

Effects of melittin on acute lung injury in mice based on TLR4/NF-κB signaling pathway

俞家旺 俞婷婷 高华新 柯洁 音弦
中国临床药理学与治疗学2024,Vol.29Issue(11) :1232-1239.DOI:10.12092/j.issn.1009-2501.2024.11.004

基于TLR4/NF-κB信号通路研究蜂毒肽对急性肺损伤小鼠的作用及机制

Effects of melittin on acute lung injury in mice based on TLR4/NF-κB signaling pathway

俞家旺 1俞婷婷 2高华新 1柯洁 3音弦3
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作者信息

  • 1. 皖南医学院弋矶山医院EICU,芜湖 241000,安徽
  • 2. 皖南医学院机能学实验实训中心,芜湖 241002,安徽
  • 3. 皖南医学院影像学院,芜湖 241002,安徽
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摘要

目的:探究蜂毒肽对LPS诱导的急性肺损伤的保护作用和机制.方法:小鼠单次气管内注射LPS(5 mg/kg)建立急性肺损伤模型.测定小鼠肺系数及肺组织湿干质量(W/D)比值,肺组织进行HE染色,检测支气管肺泡灌洗液(BALF)中炎性细胞计数及相关炎症因子的表达水平,检测血清SOD、MDA和GSH活性,免疫组化和Western blot 检测肺组织中 TLR4、NF-κB p65 和 p-NF-κB p65的表达水平.结果:蜂毒肽对LPS诱导的ALI有保护作用,其显著降低了 ALI小鼠的肺系数以及肺W/D比(P<0.05,P<0.01),减少了 BALF中炎性细胞数量和炎性因子的表达水平(P<0.05,P<0.01),改善了肺病理改变.相比模型组,蜂毒肽组小鼠血清中MDA水平显著降低(P<0.01),SOD、GSH活性明显升高(P<0.05,P<0.01).此外,蜂毒肽可显著降低TLR4表达,并抑制NF-κB p65磷酸化,减轻炎症反应(P<0.01).结论:蜂毒肽显著改善了 LPS诱导的ALI,蜂毒肽发挥的这种保护主要与其抑制TLR4/NF-κB信号通路,减轻氧化应激和炎症反应有关.

Abstract

AIM:To explore the protective effect and mechanism of melittin against LPS induced acute lung injury.METHODS:Mice were intratrache-ally injected with LPS(5 mg/kg)to establish acute lung injury model.The lung coefficient of mice and the lung wet-dry mass ratio were determined.The lung tissue was stained with HE.The number of in-flammatory cells and expression levels of related in-flammatory factors in bronchoalveolar lavage fluid(BALF)were detected.The activities of serum SOD,MDA and GSH were detected.The expression of TLR4,NF-κB p65 and p-NF-κB p65 in lung tissues were determined by immunohistochemistry and Western blot.RESULTS:Melittin had a protective ef-fect on LPS-induced ALI,as evidenced by significant-ly reduced lung coefficient,lung wet/dry mass ra-tio,the number of inflammatory cells and the ex-pression level of inflammatory factors in BALF,and improved pulmonary pathology(P<0.05,P<0.01).Compared with model group,the serum MDA level of melittin group was significantly decreased(P<0.01),while the activities of SOD and GSH were sig-nificantly increased(P<0.05,P<0.01).In addition,melittin can significantly reduce the expression of TLR4,inhibit the phosphorylation of NF-κB p65,and reduce the inflammatory response(P<0.01).CONCLUSION:Melittin can significantly improve LPS-induced ALI,and the protective effect of melit-tin is mainly related to the inhibition of TLR4/NF-κB signaling pathway and the reduction of oxidative stress and inflammation.

关键词

急性肺损伤/LPS/蜂毒肽/氧化应激/炎症

Key words

acute lung injury/LPS/melittin/oxi-dative stress/inflammation

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出版年

2024
中国临床药理学与治疗学
中国药理学会

中国临床药理学与治疗学

CSTPCD北大核心
影响因子:0.97
ISSN:1009-2501
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