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重度慢性阻塞性肺疾病患者股四头肌中的细胞因子谱

Cytokine profile in quadriceps muscles of patients with severe COPD.

作者信息

Barreiro E, Schols A M W J, Polkey M I, Galdiz J B, Gosker H R, Swallow E B, Coronell C, Gea J

机构信息

Muscle and Respiratory System Research Unit (URMAR) and Respiratory Medicine Department, IMIM-Hospital del Mar, Centro de Investigación en Red de Enfermedades Respiratorias, Pompeu Fabra University, Barcelona, Catalonia, Spain.

出版信息

Thorax. 2008 Feb;63(2):100-7. doi: 10.1136/thx.2007.078030. Epub 2007 Sep 17.

Abstract

BACKGROUND

Systemic proinflammatory cytokines and oxidative stress have been described in association with peripheral muscle wasting and weakness of patients with severe chronic obstructive pulmonary disease (COPD), but their expression in skeletal muscle is unknown. The objectives of the present study were to determine muscle protein levels of selected cytokines in patients with COPD and to study their relationships with protein carbonylation as a marker of oxidative stress, quadriceps function and exercise capacity.

METHODS

We conducted a cross sectional study in which 36 cytokines were detected using a human antibody array in quadriceps specimens obtained from 19 patients with severe COPD and seven healthy controls. Subsequently, selected cytokines (tumour necrosis factor (TNF)alpha, TNFalpha receptors I and II, interleukin (IL) 6, interferon gamma, transforming growth factor (TGF) beta and vascular endothelial growth factor (VEGF)), as well as protein carbonylation (oxidative stress index) were determined using an enzyme linked immunosorbent assay (ELISA) in all muscles.

RESULTS

Compared with controls, the vastus lateralis of patients with COPD showed significantly lower protein ELISA levels of TNFalpha, which positively correlated with their quadriceps function, TNFalpha receptor II and VEGF. Protein ELISA levels of IL6, interferon gamma and TGFbeta did not differ between patients and controls. Quadriceps protein carbonylation was greater in patients and inversely correlated with quadriceps strength among them.

CONCLUSIONS

These findings do not support the presence of a proinflammatory environment within the quadriceps muscles of clinically and weight stable patients with severe COPD, despite evidence for increased oxidative stress and the presence of muscle weakness.

摘要

背景

全身性促炎细胞因子和氧化应激已被描述与重度慢性阻塞性肺疾病(COPD)患者的外周肌肉萎缩和无力有关,但其在骨骼肌中的表达尚不清楚。本研究的目的是确定COPD患者选定细胞因子的肌肉蛋白水平,并研究它们与作为氧化应激标志物的蛋白质羰基化、股四头肌功能和运动能力之间的关系。

方法

我们进行了一项横断面研究,使用人抗体阵列在从19例重度COPD患者和7例健康对照获取的股四头肌标本中检测36种细胞因子。随后,在所有肌肉中使用酶联免疫吸附测定(ELISA)确定选定的细胞因子(肿瘤坏死因子(TNF)α、TNFα受体I和II、白细胞介素(IL)6、干扰素γ、转化生长因子(TGF)β和血管内皮生长因子(VEGF))以及蛋白质羰基化(氧化应激指数)。

结果

与对照组相比,COPD患者的股外侧肌显示TNFα的蛋白质ELISA水平显著降低,其与股四头肌功能、TNFα受体II和VEGF呈正相关。患者和对照组之间IL6、干扰素γ和TGFβ的蛋白质ELISA水平没有差异。患者的股四头肌蛋白质羰基化程度更高,且与其中的股四头肌力量呈负相关。

结论

这些发现不支持在临床和体重稳定的重度COPD患者的股四头肌内存在促炎环境,尽管有证据表明氧化应激增加和存在肌肉无力。

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