临床与病理杂志2023，Vol.43Issue(12)：2133-2143,11.DOI:10.11817/j.issn.2095-6959.2023.230072
Dectin-1受体介导肺炎克雷伯菌诱导的ARDS炎症反应及其病理特征
Dectin-1 receptor mediates ARDS inflammation induced by K.pneumoniae and its pathological features
摘要
Abstract
Objective:Immune response plays an important role in the pathophysiological mechanisms of acute respiratory distress syndrome(ARDS),and the Dectin-1 receptor mediates multiple inflammatory response pathways.This study aims to explore the characteristics of the Dectin-1 receptor in the inflammatory response induced by K.pneumoniae-induced ARDS and its correlation with pathological features. Methods:Peritoneal macrophages from C57BL/6 wild-type or Dectin-1-/-mice were extracted.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of interleukin(IL)-6,IL-1β and tumor necrosis factor-α(TNF-α)in macrophages stimulated with different multiplicities of infection(MOI)of K.pneumoniae or different concentration of lipopolysaccharide(LPS).Western blotting was performed to detect the expression of extracellular signal-regulated kinase(ERK),p38 protein,and c-Jun N-terminal kinase(JNK).Healthy wild-type mice or Dectin-1-/-mice were randomly divided into an ARDS group and a control group.The ARDS model mice were established by intratracheal infection with K.pneumoniae,while the control mice were intratracheally infected with PBS of equal volume.The 7-day survival rate of mice in 4 groups was observed.ELISA was used to detect the difference of IL-6 expression level in plasma at 3,8,24,and 48 h.HE staining was used to compare the injury of lung tissue in mice.The difference of bacterial load in lung tissue of mice was calculated and compared. Results:The expression levels of IL-6,IL-1β,and TNF-α in macrophages from Dectin-1-/-mice were higher than those from wild-type mice after stimulation with K.pneumoniae(P<0.05).After LPS stimulation,the expression of IL-6 in macrophages from Dectin-1-/-mice was significantly higher than that from wild-type mice(P<0.05).Western blotting results showed that the expression levels of ERK in macrophages from Dectin-1-/-mice were higher than those from wild-type mice at 45 and 60 min after K.pneumoniae stimulation(both P<0.05).After 30 and 60 min of stimulation,the expression levels of JNK and p38 in macrophages from Dectin-1-/-mice were higher than those from wild-type mice(all P<0.05).Within 7 days of ARDS modeling,the survival rate of Dectin-1-/-ARDS model mice was lower than that of wild-type ARDS model mice[20%(1/5)vs 100%(5/5),P<0.01].The survival rates of Dectin-1-/-and wild-type control mice were 100%(5/5).ELISA results showed that there were no significant differences in IL-6 expression levels between Dectin-1-/-ARDS model mice and wild-type ARDS model mice at 3,8,24,and 48 h after K.pneumoniae infection(all P>0.05).The expression of IL-6 in both Dectin-1-/-control mice and wild-type control mice was low after 3 to 48 h of intratracheal PBS administration.The Smith score of Dectin-1-/-ARDS model mice was higher than that of wild type ARDS model mice(P<0.05).There was no significant difference in Smith score between Dectin-1-/-control mice and wild-type control mice(P>0.05).After 24 h infection with K.pneumoniae,there was no significant difference in the amount of bacteria in lung tissue between Dectin-1-/-model mice and wild-type model mice,and between Dectin-1-/-control mice and wild-type control mice(P>0.05). Conclusion:Dectin-1 receptor is significantly correlated with the expression levels of cytokines,suggesting that the Dectin-1 receptor may play a protective role in the early stage of ARDS by reducing the expression of cytokines and thereby alleviating the severity of the inflammatory response induced by K.pneumoniae-induced ARDS.关键词
Dectin-1受体/肺炎克雷伯菌/急性呼吸窘迫综合征/炎症反应Key words
Dectin-1 receptor/K.pneumoniae/acute respiratory distress syndrome/inflammatory response引用本文复制引用
王丽辉,施安,唐佳佳,施志强,李卉,吴卉,艾田逸,朱铭力,余跃天..Dectin-1受体介导肺炎克雷伯菌诱导的ARDS炎症反应及其病理特征[J].临床与病理杂志,2023,43(12):2133-2143,11.基金项目
多脏器衰竭预警与干预教育部重点实验室开放课题资助项目(2023KF07) （2023KF07）
湖州市智能药学与个体化治疗重点实验室开放基金(HZKF-20240101) （HZKF-20240101）
广西急性呼吸窘迫综合征诊治研究重点实验室开放基金(ZZH2020013-3).This work was supported by the Project of the Key Laboratory of Multiple Organ Failure,Ministry of Education(2023KF07),the Key Laboratory of Intelligent Pharmacy and Individualized Treatment in Huzhou City(HZKF-20240101),and the Guangxi Key Laboratory for Diagnosis and Treatment of Acute Respiratory Distress Syndrome(ZZH2020013-3),China. （ZZH2020013-3）
