脂多糖所致小鼠急性肺损伤中乙酰肝素酶的变化及其对肺泡巨噬细胞极化的影响
Changes of heparanase and its effect on the polarization of alveolar macrophage in acute lung injury induced by lipopolysaccharide in mice
张雁林 1赵怡然 1陈明 1李晓 1郑亦沐 1关里 1李树强1
作者信息
- 1. 北京大学第三医院职业医学研究中心,北京 100191
- 折叠
摘要
目的 研究脂多糖(LPS)所致急性呼吸窘迫综合征(ARDS)发病中肺泡巨噬细胞(AM)乙酰肝素酶(HPSE)的变化及其对AM功能的调节作用.方法 通过气管滴注LPS复制小鼠ARDS模型,检测小鼠肺支气管肺泡灌洗液(BALF)中巨噬细胞HPSE转录和酶活性以及促炎因子肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的表达,通过给予HPSE抑制剂OGT2115(15 mg/kg)研究HPSE对肺泡巨噬细胞促炎因子表达的影响.结果 小鼠经LPS染毒后,BALF中巨噬细胞HPSE转录表达和酶活性明显增加,与LPS剂量显著相关.巨噬细胞TNF-α和IL-1β表达水平明显增加,表明巨噬细胞发生M1型促炎极化.HPSE抑制剂OGT2115可抑制巨噬细胞促炎因子表达,提示HPSE可调节巨噬细胞的M1型转化.结论 LPS染毒所致小鼠急性肺损伤发病中,巨噬细胞HPSE表达增加,并进一步调控AM向M1型极化,促进ARDS发生发展.
Abstract
Objective To study the changes of heparanase(HPSE)in alveolar macrophage(AM)during the pathogenesis of acute respiratory distress syndrome(ARDS)induced by lipopolysaccharide(LPS)and its regulatory effect on AM function.Methods The ARDS model was reproduced by tracheal instillation of LPS in mice.HPSE transcription,enzyme activity and pro-inflammatory factor(TNF-α,IL-1β)expression of macrophage in BALF were detected.The effect of HPSE on the expression of pro-inflammatory factor in AM was studied through HPSE inhibitor OGT2115(15 mg/kg).Results The HPSE transcription and enzyme activity in macrophage from BALF were significantly increased after LPS exposure,and there was a significant correlation with LPS dosage.Similar to the changes of HPSE,the transcription of pro-inflammatory factors TNF-α and IL-1β in macrophage also increased significantly,indicating M1-type pro-inflammatory polarization in macrophages.HPSE inhibitor OGT2115 could inhibit the expression of pro-inflammatory factors in macrophages,suggesting that HPSE could regulate the M1 transformation of macrophages.Conclusion HPSE expression in macrophages was increased in the pathogenesis of acute lung injury induced by LPS,and HPSE further regulated AM polarization to M1 type and promoted the development of ARDS.
关键词
急性呼吸窘迫综合征(ARDS)/脂多糖(LPS)/肺泡巨噬细胞(AM)/乙酰肝素酶(HPSE)Key words
acute respiratory distress syndrome(ARDS)/lipopolysaccharide(LPS)/alveolar macrophage(AM)/heparanase(HPSE)引用本文复制引用
基金项目
国家自然科学基金面上项目(81773374)
北京市自然科学基金面上项目(7182179)
出版年
2024
NETL
NSTL
万方数据