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半胱氨酸对轻度急性加重期慢性阻塞性肺疾病患者循环中miR-21、白细胞介素-8、可溶性晚期糖基化终末产物受体及晚期糖基化终末产物水平的影响:一项初步研究

Carbocysteine Modifies Circulating miR-21, IL-8, sRAGE, and fAGEs Levels in Mild Acute Exacerbated COPD Patients: A Pilot Study.

作者信息

Ferraro Maria, Di Vincenzo Serena, Sangiorgi Claudia, Leto Barone Stefania, Gangemi Sebastiano, Lanata Luigi, Pace Elisabetta

机构信息

Institute for Biomedical Research and Innovation (IRIB)-Consiglio Nazionale delle Ricerche, 90146 Palermo, Italy.

Institute of Translational Pharmacology (IFT)-National Research Council, 90146 Palermo, Italy.

出版信息

Pharmaceuticals (Basel). 2022 Feb 11;15(2):218. doi: 10.3390/ph15020218.

Abstract

Patients with Chronic Obstructive Pulmonary Disease (COPD) periodically experience acute exacerbation (AECOPD). Carbocysteine represents a valid add on therapy in COPD by exerting antioxidant and anti-inflammatory activities. The in vivo effects of carbocysteine on inflammatory markers are not yet fully understood. The aims of this study were to assess: (i) miR-21, IL-8, soluble Receptor for Advanced Glycation End Products (sRAGE), and fluorescent Advanced Glycation End Products (fAGEs) in control subjects ( = 9), stable ( = 9), and AECOPD patients ( = 24); and (ii) whether carbocysteine modifies these markers and the functional parameters in mild AECOPD patients. Mild AECOPD patients received or not carbocysteine along with background inhalation therapy for 20 days. At the onset and at the end of the observation period, the following parameters were evaluated: FEV1, FEF25-75%, CAT questionnaire; miR-21 by Real Time PCR; IL-8 and sRAGE by ELISA; and fAGEs by spectro-fluorescence method. COPD patients showed higher levels of miR-21, IL-8, fAGEs and lower levels of sRAGE compared to that of controls. miR-21 inversely correlated with FEV1. IL-8 and fAGEs were significantly different in stable and exacerbated COPD patients. Carbocysteine improved symptoms, FEV1 and FEF25-75%, increased sRAGE, and reduced miR-21, IL-8, and fAGEs in mild AECOPD patients. The present study provides compelling evidence that carbocysteine may help to manage mild AECOPD by downregulating some parameters of systemic inflammation.

摘要

慢性阻塞性肺疾病(COPD)患者会周期性地经历急性加重期(AECOPD)。羧甲司坦通过发挥抗氧化和抗炎活性,是COPD一种有效的附加治疗药物。羧甲司坦对炎症标志物的体内作用尚未完全明确。本研究的目的是评估:(i)对照组(n = 9)、稳定期(n = 9)和AECOPD患者(n = 24)中的miR-21、白细胞介素-8(IL-8)、可溶性晚期糖基化终末产物受体(sRAGE)和荧光晚期糖基化终末产物(fAGEs);以及(ii)羧甲司坦是否会改变轻度AECOPD患者的这些标志物和功能参数。轻度AECOPD患者在接受背景吸入治疗的同时,接受或不接受羧甲司坦治疗20天。在观察期开始和结束时,评估以下参数:第1秒用力呼气容积(FEV1)、用力呼气中期流速(FEF25-75%)、慢性阻塞性肺疾病评估测试(CAT)问卷;通过实时聚合酶链反应检测miR-21;通过酶联免疫吸附测定法检测IL-8和sRAGE;通过光谱荧光法检测fAGEs。与对照组相比,COPD患者的miR-21、IL-8、fAGEs水平更高,而sRAGE水平更低。miR-21与FEV1呈负相关。稳定期和加重期COPD患者的IL-8和fAGEs存在显著差异。羧甲司坦改善了轻度AECOPD患者的症状、FEV1和FEF25-75%,增加了sRAGE,并降低了miR-21、IL-8和fAGEs。本研究提供了令人信服的证据,表明羧甲司坦可能通过下调全身炎症的一些参数来帮助管理轻度AECOPD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df7c/8880736/7ba309e2df10/pharmaceuticals-15-00218-g001.jpg

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