COPD 患者中晚期糖基化终产物可溶性受体：与肺气肿和慢性肺源性心脏病的关系：一项病例对照研究。
Soluble receptor for advanced glycation end products in COPD: relationship with emphysema and chronic cor pulmonale: a case-control study.
机构信息
Department of Medical and Surgical Critical Care, University of Florence, 50134 Florence, Italy.
出版信息
Respir Res. 2011 Mar 30;12(1):37. doi: 10.1186/1465-9921-12-37.
BACKGROUND
The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction receptor that can initiate and perpetuate inflammation. Its soluble isoform (sRAGE) acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation. With the present study, we aimed at determining whether circulating sRAGE is correlated with emphysema and chronic cor pulmonale in chronic obstructive pulmonary disease (COPD).
METHODS
In 200 COPD patients and 201 age- and sex-matched controls, we measured lung function by spirometry, and sRAGE by ELISA method. We also measured the plasma levels of two RAGE ligands, N-epsilon-carboxymethyl lysine and S100A12, by ELISA method. In the COPD patients, we assessed the prevalence and severity of emphysema by computed tomography (CT), and the prevalence of chronic cor pulmonale by echocardiography. Multiple quantile regression was used to assess the effects of emphysema, chronic cor pulmonale, smoking history, and comorbid conditions on the three quartiles of sRAGE.
RESULTS
sRAGE was significantly lower (p = 0.007) in COPD patients (median 652 pg/mL, interquartile range 484 to 1076 pg/mL) than in controls (median 869 pg/mL, interquartile range 601 to 1240 pg/mL), and was correlated with the severity of emphysema (p < 0.001), the lower the level of sRAGE the greater the degree of emphysema on CT. The relationship remained statistically significant after adjusting for smoking history and comorbid conditions. In addition, sRAGE was significantly lower in COPD patients with chronic cor pulmonale than in those without (p = 0.002). Such difference remained statistically significant after adjusting for smoking history, comorbidities, and emphysema severity. There was no significant difference in the plasma levels of the two RAGE ligands between cases and controls.
CONCLUSIONS
sRAGE is significantly lower in patients with COPD than in age- and sex-matched individuals without airflow obstruction. Emphysema and chronic cor pulmonale are independent predictors of reduced sRAGE in COPD.
背景
晚期糖基化终产物受体（RAGE）是一种多配体信号转导受体，可引发并持续炎症反应。其可溶性异构体（sRAGE）作为 RAGE 配体的诱饵受体，被认为能对抗炎症反应。本研究旨在确定循环 sRAGE 是否与慢性阻塞性肺疾病（COPD）中的肺气肿和慢性肺源性心脏病有关。
方法
在 200 例 COPD 患者和 201 例年龄和性别匹配的对照组中，我们通过肺量计测量肺功能，并通过 ELISA 方法测量 sRAGE。我们还通过 ELISA 方法测量了两种 RAGE 配体，N-ε-羧甲基赖氨酸和 S100A12 的血浆水平。在 COPD 患者中，我们通过计算机断层扫描（CT）评估肺气肿的患病率和严重程度，并通过超声心动图评估慢性肺源性心脏病的患病率。采用多元分位数回归评估肺气肿、慢性肺源性心脏病、吸烟史和合并症对 sRAGE 三个四分位数的影响。
结果
与对照组（中位数 869pg/mL，四分位距 601-1240pg/mL）相比，COPD 患者（中位数 652pg/mL，四分位距 484-1076pg/mL）sRAGE 显著降低（p=0.007），且与肺气肿严重程度相关（p<0.001），sRAGE 水平越低，CT 上肺气肿程度越严重。调整吸烟史和合并症后，该关系仍具有统计学意义。此外，与无慢性肺源性心脏病的 COPD 患者相比，有慢性肺源性心脏病的 COPD 患者的 sRAGE 显著降低（p=0.002）。调整吸烟史、合并症和肺气肿严重程度后，这种差异仍具有统计学意义。病例组和对照组之间两种 RAGE 配体的血浆水平无显著差异。
结论
与无气流阻塞的年龄和性别匹配个体相比，COPD 患者的 sRAGE 显著降低。肺气肿和慢性肺源性心脏病是 COPD 患者 sRAGE 降低的独立预测因子。
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