低氧诱导因子在COPD合并曲霉菌感染中调控吞噬和自噬相关机制  

Mechanism of hypoxia-inducible factor in regulating phagocytosis and autophagy in COPD complicated with Aspergillus infection

作　　者：胡晟 张群 孙建 孙磊[2] HU Sheng;ZHANG Qun;SUN Jian;SUN Lei(Yancheng First People's Hospital,Yancheng,Jiangsu 224000,China;不详)

机构地区：[1]盐城市第一人民医院呼吸与危重症医学科,江苏盐城224000 [2]南京大学医学院附属鼓楼医院呼吸与危重症医学科,江苏南京210008

出　　处：《中华医院感染学杂志》2023年第7期981-985,共5页Chinese Journal of Nosocomiology

基　　金：江苏省医学重点学科基金资助项目(ZDXKB2019012)。

摘　　要：目的探讨低氧诱导因子1α(HIF-1α)在慢性阻塞性肺病(COPD)合并曲霉菌感染中调控巨噬细胞吞噬相关机制。方法收集2020年5月-2022年4月在盐城第一人民医院就诊的单纯慢性阻塞性肺病患者30例、慢性阻塞性肺病合并曲霉菌感染患者27例和健康志愿者30名,检测上述研究对象巨噬细胞吞噬功能及吞噬蛋白活化水平;采用曲霉菌转染人单核巨噬细胞THP-1并检测细胞中吞噬相关受体表达并分析。结果COPD合并曲霉菌感染组的炎性细胞总数高于单纯COPD组和对照组,巨噬细胞占比和PI低于单纯COPD组和对照组(P<0.05);COPD合并曲霉菌感染组研究对象的HIF-1αmRNA及蛋白高于单纯COPD组和对照组,MyD88、PI3K、TLR2、Beclin-1、LC3-I、LC3-Ⅱ的mRNA及蛋白相对表达水平低于单纯COPD组(P<0.05);曲霉菌转染THP-1后,模型组、阻断组的Beclin-1、LC3-I、LC3-Ⅱ的mRNA及蛋白相对表达水平高于对照组(P<0.05);阻断组的Beclin-1、LC3-I、LC3-Ⅱ的mRNA及蛋白相对表达水平高于模型组(P<0.05)。结论低氧诱导因子1α能够调节COPD合并曲霉菌感染患者的吞噬功能,低氧诱导因子1α在曲霉菌刺激巨噬细胞诱导吞噬和自噬活化的过程中具有重要作用,推测此可能为机体的一种自身免疫机制。OBJECTIVE To investigate the mechanism of hypoxia-inducible factor 1α(HIF-1α)in the regulation of macrophage phagocytosis and autophagy in chronic obstructive pulmonary disease(COPD)complicated with Aspergillus infection.METHODS A total of 30 patients with simple chronic obstructive pulmonary disease,27 patients with chronic obstructive pulmonary disease complicated by Aspergillus infection and 30 healthy volunteers who were treated in Yancheng First People′s Hospital from May 2020 to Apr 2022 were enrolled.The phagocytosis function of macrophages and the activation level of phagocytosis protein in all research subjects were detected.Aspergillus was used to infect human mononuclear macrophages THP-1 and the expression of phagocytosis-related receptors in the cells were analyzed.RESULTS The total number of inflammatory cells in the COPD-combined Aspergillus infection group was higher than that in the simple COPD group and the control group,and the proportion of macrophages and PI were lower than those in the simple COPD group and the control group(P<0.05).The mRNA and protein levels of HIF-1a in the study subjects of the COPD-combined Aspergillus infection group were higher than that of the simple COPD group and the control group;and the relative expression levels of mRNA and protein of MyD88,PI3K,TLR2,Beclin-1,LC3-I,LC3-Ⅱwere lower than that in the simple COPD group(P<0.05).After THP-1 infected by Aspergillus,the relative expression levels of mRNA and protein of Beclin-1,LC3-I,and LC3-Ⅱin the model group and blocking group were higher than those in the control group(P<0.05);the relative expression levels of mRNA and protein of Beclin-1,LC3-I,and LC3-Ⅱin the blocking group were higher than that in the model group(P<0.05).CONCLUSION Hypoxia-inducible factor 1αcan regulate the phagocytic function in patients with COPD complicated with Aspergillus infection.Hypoxia-inducible factor 1αplays an important role in the process of Aspergillus-stimulated macrophages to induce phagocytosis and autophagy activatio

关 键 词：低氧诱导因子1Α 慢性阻塞性肺病 曲霉菌 吞噬细胞 吞噬和自噬 

分 类 号：R563[医药卫生—呼吸系统]