TREM-1/NF-κB通路在二甲双胍调控小鼠急性肺损伤中的作用研究
The role of TREM-1/NF-κB pathway in regulation of metformin on mouse acute lung injury
韦运富 1周灿 1李锐 2罗宇涛 1黄仲恩 1任翔 1孙国瑛1
作者信息
- 1. 湖南师范大学医学院,长沙 410013
- 2. 湖南师范大学树达学院,长沙 410013
- 折叠
摘要
目的:观察二甲双胍对脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠模型中的髓样细胞表达的触发受体1(TREM-1)的作用,并探讨二甲双胍是否可通过TREM-1/核因子(NF)-κB通路减轻小鼠的ALI.方法:首先通过腹腔注射10 mg/kg LPS建立ALI小鼠模型,并采用二甲双胍或TREM-1受体拮抗剂干预,观察二甲双胍对ALI小鼠TREM-1表达的影响;检测灌洗液(BALF)中的总蛋白水平、总细胞数量和中性粒细胞数量、乳酸脱氢酶(LDH)和髓过氧化物酶(MPO)及肺组织湿/干比重分析,通过 Real time-PCR检测 NF-κB和 TREM-1 mRNA 的表达,Western Blot检测 小鼠肺组织NF-κB、IL-18、IL-1β、TNF-α、TREM-1蛋白的表达.结果:研究结果显示,二甲双胍可降低ALI小鼠肺组织TREM-1的表达水平.拮抗TREM-1后,二甲双胍可减轻ALI小鼠肺组织病理损伤、蛋白渗出和中性粒细胞浸润;抑制NF-κB、IL-18、IL-1β、TNF-α等炎症因子的表达.结论:二甲双胍可通过减少炎症因子表达,降低血管通透性与炎症细胞的浸润,从而减轻 LPS 诱导的 ALI,其作用机制可能与TREM-1/NF-κB通路有关.
Abstract
Objective This study was designed to examine the effect of metformin on triggering receptors expressed on myeloid cells-1(TREM-1)in a lipopolysaccharide(LPS)induced acute lung injury(ALI)mouse model and explore whether metformin uti-lizes TREM-1/NF-κB pathway to reduce ALI in mice.Methods First of all,an ALI mouse model was established by intraperito-neal injection of 10 mg/kg LPS,and intervention with metformin or TREM-1 receptor antagonist was used to examine the effect of metformin on TREM-1 expression in ALI mice.Total protein level,total cell and neutrophil count,lactate dehydrogenase(LDH)and myeloperoxidase(MPO)were determined in the lavage fluid(BALF),and the wet/dry specific gravity of lung tissues were as-sessed.NF-κB and TREM-1 mRNA expression was assessed through Real time-PCR,while NF-κB,IL-18,IL-1β,TNF-α and TREM-1 protein expression levels were measured by Western blots.Results Our results showed that metformin reduced the ex-pression of TREM-1 in the lung tissue of ALI mice.After antagonizing TREM-1,metformin could alleviate pathological damage,protein exudation,and neutrophil infiltration in lung tissue,and expression of NF-κB,IL-18,IL-1β,TNF-α was inhibited.Con-clusion Metformin can reduce the expression of inflammatory factors,vascular permeability,and infiltration of inflammatory cells,thereby alleviating LPS-induced ALI,and its mechanism may be related to TREM-1/NF-κ B pathway.
关键词
急性肺损伤/二甲双胍/髓样细胞表达的触发受体1(TREM-1)/核因子(NF)-κBKey words
acute lung injury/metformin/triggering receptors expressed on myeloid cells-1(TREM-1)/nuclear factor-κB引用本文复制引用
基金项目
湖南省卫生健康委2023年度科研计划课题(D202301019729)
湖南省大学生创新创业训练计划项目(S202212652013)
出版年
2024
NETL
NSTL
万方数据