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-kB signaling pathway

作　　者：俞家旺 俞婷婷[2] 高华新 柯洁 音弦 YU Jiawang;YU Tingting;GAO Huaxin;KE Jie;YIN Xian(EICU,Yijishan Hospital of Wannan Medical College,Wuhu 241000,Anhui,China;Department of Functional Experiment Training Center,Wannan Medical College,Wuhu 241002,Anhui,China;School of Medical Imag-ing,Wannan Medical College,Wuhu 241002,Anhui,China)

机构地区：[1]皖南医学院弋矶山医院EICU,安徽芜湖241000 [2]皖南医学院机能学实验实训中心,安徽芜湖241002 [3]皖南医学院影像学院,安徽芜湖241002

出　　处：《中国临床药理学与治疗学》2024年第11期1232-1239,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：2023年安徽省高等学校科学研究项目自然科学类重点项目(2023AH051755);2021年皖南医学院校中青年自然科学项目(WK2021F14);2022年安徽省危重症呼吸疾病临床医学研究中心校级开放课题(LC202208);2020年国家级大学生创新训练项目(202010368046);2021年安徽省大学生创新创业训练计划(S202110368121)。

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。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 

分 类 号：R965.2[医药卫生—药理学]