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血清中 α-Klotho 水平降低与间质性肺异常个体的肺功能下降有关。

Lower levels of α-Klotho in serum are associated with decreased lung function in individuals with interstitial lung abnormalities.

机构信息

Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", México city, Mexico.

Facultad de Ciencias, Universidad Nacional Autónoma de México, México city, Mexico.

出版信息

Sci Rep. 2019 Jul 25;9(1):10801. doi: 10.1038/s41598-019-47199-0.

DOI:10.1038/s41598-019-47199-0
PMID:31346213
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6658567/
Abstract

Interstitial lung abnormalities (ILA) represent aging-associated bilateral interstitial abnormalities in nondependent areas of the lung. However, the aging mechanisms associated with ILA remain uncertain. α-Klotho is an anti-aging molecule that decreases progressively with age, and abnormally low circulating levels of this protein have been revealed in several chronic-degenerative diseases. In this study, we evaluated α-Klotho serum concentrations in individuals with ILA, and examined whether its levels were associated with pulmonary function decline. α-Klotho was measured by ELISA in 50 respiratory asymptomatic adults with ILA and 150 healthy individuals over 60 years. Compared with controls, ILA subjects were predominantly older males, and showed lower lung diffusing capacity (DLCO), higher desaturation after exercise, and higher concentrations of serum matrix metalloprotease-7 (6.24 ± 4.1 versus 4.3 ± 1.7 ng/ml; p = 0.002). No differences were found in serum concentrations of α-Klotho. However, lower levels of this protein in ILA significantly correlated with lower values of forced vital capacity (Rho = 0.39; p = 0.005), forced expiratory volume in one second (Rho = 0.39; p = 0.005), and DLCO (Rho = 0.29, p = 0.04). These findings suggest that decreased concentrations of α-Klotho may be a predictive biomarker of accelerated decline of lung function in individuals with ILA.

摘要

肺间质异常(ILA)代表非依赖区肺的与年龄相关的双侧间质异常。然而,与 ILA 相关的衰老机制尚不确定。α-Klotho 是一种抗衰老分子,其水平随年龄逐渐降低,在几种慢性退行性疾病中发现这种蛋白的循环水平异常降低。在这项研究中,我们评估了 ILA 个体的α-Klotho 血清浓度,并检查了其水平是否与肺功能下降有关。通过 ELISA 法在 50 名有 ILA 且无呼吸系统症状的成年人和 150 名 60 岁以上的健康个体中测量了α-Klotho。与对照组相比,ILA 组主要为年龄较大的男性,且弥散量(DLCO)较低,运动后缺氧程度较高,以及基质金属蛋白酶-7(matrix metalloprotease-7,MMP-7)的血清浓度较高(6.24±4.1 与 4.3±1.7ng/ml;p=0.002)。α-Klotho 的血清浓度无差异。然而,ILA 中这种蛋白的较低水平与用力肺活量(forced vital capacity,FVC)(Rho=0.39;p=0.005)、一秒用力呼气容积(forced expiratory volume in one second,FEV1)(Rho=0.39;p=0.005)和 DLCO 显著负相关(Rho=0.29,p=0.04)。这些发现表明,α-Klotho 浓度降低可能是 ILA 个体肺功能加速下降的预测生物标志物。

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