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循环成纤维细胞对急性肺损伤/急性呼吸窘迫综合征小鼠模型损伤修复的抑制作用。

Inhibitory effect of circulating fibrocytes on injury repair in acute lung injury/acute respiratory distress syndrome mice model.

机构信息

Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Department of Hematology, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

出版信息

J Cell Biochem. 2018 Nov;119(10):7982-7990. doi: 10.1002/jcb.26664. Epub 2018 Jun 22.

Abstract

The study was aimed to explore the functions of circulating fibrocytes (CFs) on injury repair in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) mice model and its clinical value as a biomarker for ALI/ARDS. ALI/ARDS mice model was established by intratracheal instillation of lipopolysaccharide (LPS). Mononuclear cells were isolated from peripheral blood of ALI/ARDS model and flow cytometry was used to measure CFs defined as cells positive for CD45 and collagen-1. Histological changes of lung tissues were evaluated by H&E staining and Masson's trichrome staining. The correlations of CFs counts with damnification of lung tissue and the severity of pulmonary fibrosis were evaluated by Pearson correlation analyses. Western blot was used to detect the protein expression of collagen-1. ELISA was applied to determine cytokine CXCL12 concentration. Clinical relevance between CFs and ALI/ARDS was investigated. The greater number of CFs in the ALI/ARDS group implied higher degree of lung injury and more severe pulmonary fibrosis. The protein expression of collagen-1 and concentration of cytokine CXCL12 in ALI/ARDS group were higher than that in control group. Clinical and prognostic analysis revealed the higher injury degree and death rates in ALI/ARDS group than those in control group, and identified a greater severity and mortality for patients with ARDS than those with ALI. ROC curve analysis indicated the counts of CFs greater than 5.85% can predict death rates with AUC = 0.928. CFs had an inhibitory effect on injury repair in ALI/ARDS mice model. This might be unfavorable as a clinical marker for progression of ALI/ARDS.

摘要

本研究旨在探讨循环成纤维细胞(CFs)在急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)小鼠模型中的损伤修复功能及其作为 ALI/ARDS 生物标志物的临床价值。通过气管内滴注脂多糖(LPS)建立 ALI/ARDS 小鼠模型。从 ALI/ARDS 模型的外周血中分离单核细胞,并通过流式细胞术测量 CFs,CFs 定义为 CD45 和胶原蛋白-1 阳性的细胞。通过 H&E 染色和 Masson 三色染色评估肺组织的组织学变化。通过 Pearson 相关分析评估 CFs 计数与肺组织损伤和肺纤维化严重程度的相关性。使用 Western blot 检测胶原蛋白-1 的蛋白表达。应用 ELISA 测定细胞因子 CXCL12 的浓度。研究 CFs 与 ALI/ARDS 之间的临床相关性。在 ALI/ARDS 组中 CFs 的数量越多,意味着肺损伤程度越高,肺纤维化越严重。ALI/ARDS 组中胶原蛋白-1 的蛋白表达和细胞因子 CXCL12 的浓度均高于对照组。临床和预后分析显示,ALI/ARDS 组的损伤程度和死亡率均高于对照组,且 ARDS 患者的严重程度和死亡率均高于 ALI 患者。ROC 曲线分析表明,CFs 计数大于 5.85%可预测死亡率,AUC 为 0.928。CFs 对 ALI/ARDS 小鼠模型中的损伤修复具有抑制作用。这可能不利于作为 ALI/ARDS 进展的临床标志物。

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