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学科主题临床医学
Extracellular Histones Play an Inflammatory Role in Acid Aspiration-induced Acute Respiratory Distress Syndrome
Zhang, Yanlin1; Wen, Zongmei2; Guan, Li1; Jiang, Ping3; Gu, Tao4; Zhao, Jinyuan1; Lv, Xin2; Wen, Tao5
刊名ANESTHESIOLOGY
2015
DOI10.1097/ALN.0000000000000429
122期:1页:127-139
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Anesthesiology
资助者National Natural Science Foundation of China, Beijing, People&prime ; s Republic of China ; Beijing Municipal Health System High-level Talent Training Project, Beijing, People&prime ; s Republic of China ; Shanghai Municipal Committee of Science and Technology, Shanghai, People&prime ; s Republic of China ; Pujiang Talent Program, Shanghai, People&prime ; s Republic of China ; National Natural Science Foundation of China, Beijing, People&prime ; s Republic of China ; Beijing Municipal Health System High-level Talent Training Project, Beijing, People&prime ; s Republic of China ; Shanghai Municipal Committee of Science and Technology, Shanghai, People&prime ; s Republic of China ; Pujiang Talent Program, Shanghai, People&prime ; s Republic of China
研究领域[WOS]Anesthesiology
关键词[WOS]ACUTE LUNG INJURY ; LIVER-INJURY ; CIRCULATING NUCLEOSOMES ; THROMBIN GENERATION ; MICE ; HEPARIN ; SEPSIS ; MEDIATORS ; BINDING ; TLR4
英文摘要

Background: Systemic inflammation is a key feature in acid aspiration-induced acute respiratory distress syndrome (ARDS), but the factors that trigger inflammation are unclear. The authors hypothesize that extracellular histones, a newly identified inflammatory mediator, play important roles in the pathogenesis of ARDS.

Methods: The authors used a hydrochloric acid aspiration-induced ARDS model to investigate whether extracellular histones are pathogenic and whether targeting histones are protective. Exogenous histones and antihistone antibody were administered to mice. Heparin can bind to histones, so the authors studied whether heparin could protect from ARDS using cell and mouse models. Furthermore, the authors analyzed whether extracellular histones are clinically involved in ARDS patients caused by gastric aspiration.

Results: Extracellular histones in bronchoalveolar lavage fluid of acid-treated mice were significantly higher (1.832 0.698) at 3 h after injury than in sham-treated group (0.63 +/- 0.153; P = 0.0252, n = 5 per group). Elevated histones may originate from damaged lung cells and neutrophil infiltration. Exogenous histones aggravated lung injury, whereas antihistone antibody markedly attenuated the intensity of ARDS. Notably, heparin provided a similar protective effect against ARDS. Analysis of plasma from ARDS patients (n = 21) showed elevated histones were significantly correlated with the degree of ARDS and were higher in nonsurvivors (2.723 +/- 0.2933, n = 7) than in survivors (1.725 +/- 0.1787, P = 0.006, n = 14).

Conclusion: Extracellular histones may play a contributory role toward ARDS by promoting tissue damage and systemic inflammation and may become a novel marker reflecting disease activity. Targeting histones by neutralizing antibody or heparin shows potent protective effects, suggesting a potentially therapeutic strategy.

语种英语
所属项目编号81272142 ; 81372094 ; 81400052 ; 14ZR1434400 ; 14PJD030
资助者National Natural Science Foundation of China, Beijing, People&prime ; s Republic of China ; Beijing Municipal Health System High-level Talent Training Project, Beijing, People&prime ; s Republic of China ; Shanghai Municipal Committee of Science and Technology, Shanghai, People&prime ; s Republic of China ; Pujiang Talent Program, Shanghai, People&prime ; s Republic of China ; National Natural Science Foundation of China, Beijing, People&prime ; s Republic of China ; Beijing Municipal Health System High-level Talent Training Project, Beijing, People&prime ; s Republic of China ; Shanghai Municipal Committee of Science and Technology, Shanghai, People&prime ; s Republic of China ; Pujiang Talent Program, Shanghai, People&prime ; s Republic of China
WOS记录号WOS:000351737100021
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67762
专题北京大学第三临床医学院_职业病科
作者单位1.Peking Univ, Res Ctr Occupat Med, Hosp 3, Beijing 100871, Peoples R China
2.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Anesthesiol, Shanghai 200092, Peoples R China
3.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Emergency, Shanghai 200092, Peoples R China
4.First Hosp Qinhuangdao, Dept Oncol, Qinhuangdao, Hebei Province, Peoples R China
5.Capital Med Univ, Beijing Youan Hosp, Beijing Inst Hepatol, Beijing 100069, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Yanlin,Wen, Zongmei,Guan, Li,et al. Extracellular Histones Play an Inflammatory Role in Acid Aspiration-induced Acute Respiratory Distress Syndrome[J]. ANESTHESIOLOGY,2015,122(1):127-139.
APA Zhang, Yanlin.,Wen, Zongmei.,Guan, Li.,Jiang, Ping.,Gu, Tao.,...&Wen, Tao.(2015).Extracellular Histones Play an Inflammatory Role in Acid Aspiration-induced Acute Respiratory Distress Syndrome.ANESTHESIOLOGY,122(1),127-139.
MLA Zhang, Yanlin,et al."Extracellular Histones Play an Inflammatory Role in Acid Aspiration-induced Acute Respiratory Distress Syndrome".ANESTHESIOLOGY 122.1(2015):127-139.
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