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血清 AGE/RAGEs 作为特发性肺纤维化的潜在生物标志物。

Serum AGE/RAGEs as potential biomarker in idiopathic pulmonary fibrosis.

机构信息

Pneumology Research Group, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Biomedical Research Network Centers in Respiratory Diseases (CIBERES), Barcelona, Spain.

出版信息

Respir Res. 2018 Nov 8;19(1):215. doi: 10.1186/s12931-018-0924-7.

Abstract

BACKGROUND

The soluble receptor for advanced glycation end-products (sRAGE) has been suggested that it acts as a decoy for capturing advanced glycation end-products (AGEs) and inhibits the activation of the oxidative stress and apoptotic pathways. Lung AGEs/sRAGE is increased in idiopathic pulmonary fibrosis (IPF). The objective of the study was to evaluate the AGEs and sRAGE levels in serum as a potential biomarker in IPF.

METHODS

Serum samples were collected from adult patients: 62 IPF, 22 chronic hypersensitivity pneumonitis (cHP), 20 fibrotic non-specific interstitial pneumonia (fNSIP); and 12 healthy controls. In addition, 23 IPF patients were re-evaluated after 3-year follow-up period. Epidemiological and clinical features were recorded: age, sex, smoking habits, and lung function. AGEs and sRAGE were evaluated by ELISA, and the results were correlated with pulmonary functional test values.

RESULTS

IPF and cHP groups presented a significant increase of AGE/sRAGE serum concentration compared with fNSIP patients. Moreover, an inverse correlation between AGEs and sRAGE levels were found in IPF, and serum sRAGE at diagnosis correlated with FVC and DLCO values. Additionally, changes in serum AGEs and sRAGE correlated with % change of FVC, DLCO and TLC during the follow-up. sRAGE levels below 428.25 pg/ml evolved poor survival rates.

CONCLUSIONS

These findings demonstrate that the increase of AGE/sRAGE ratio is higher in IPF, although the levels were close to cHP. AGE/sRAGE increase correlates with respiratory functional progression. Furthermore, the concentration of sRAGE in blood stream at diagnosis and follow-up could be considered as a potential prognostic biomarker.

摘要

背景

可溶性晚期糖基化终产物受体(sRAGE)被认为可以作为捕获晚期糖基化终产物(AGEs)的诱饵,并抑制氧化应激和凋亡途径的激活。特发性肺纤维化(IPF)患者的肺 AGE/sRAGE 增加。本研究旨在评估血清中 AGEs 和 sRAGE 水平作为 IPF 的潜在生物标志物。

方法

收集成年患者的血清样本:62 例 IPF、22 例慢性过敏性肺炎(cHP)、20 例纤维化非特异性间质性肺炎(fNSIP)和 12 例健康对照。此外,23 例 IPF 患者在 3 年随访后进行了重新评估。记录了流行病学和临床特征:年龄、性别、吸烟习惯和肺功能。通过 ELISA 评估 AGEs 和 sRAGE,结果与肺功能测试值相关。

结果

与 fNSIP 患者相比,IPF 和 cHP 组的血清 AGE/sRAGE 浓度显著升高。此外,在 IPF 中发现 AGEs 和 sRAGE 水平呈负相关,并且诊断时的血清 sRAGE 与 FVC 和 DLCO 值相关。此外,血清 AGEs 和 sRAGE 的变化与随访期间 FVC、DLCO 和 TLC 的变化呈正相关。sRAGE 水平低于 428.25 pg/ml 的患者生存率较差。

结论

这些发现表明,尽管 IPF 中的 AGE/sRAGE 比值升高,但与 cHP 相比,水平接近。AGE/sRAGE 增加与呼吸功能进展相关。此外,在诊断和随访时血液中 sRAGE 的浓度可被视为潜在的预后生物标志物。

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