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肺气肿患者的肺成纤维细胞在培养中显示出增殖速率降低。

Lung fibroblasts from patients with emphysema show a reduced proliferation rate in culture.

作者信息

Holz O, Zühlke I, Jaksztat E, Müller K C, Welker L, Nakashima M, Diemel K D, Branscheid D, Magnussen H, Jörres R A

机构信息

Research Laboratory, Hospital Grosshansdorf, Centre for Pneumology and Thoracic Surgery, Wöhrendamm 80, D-22927, Grosshansdorf, Germany.

出版信息

Eur Respir J. 2004 Oct;24(4):575-9. doi: 10.1183/09031936.04.00143703.

Abstract

Emphysema is characterised by a loss of alveolar structure, as reflected in elastic recoil and gas exchange. As fibroblasts play a key role in the maintenance of structure, the current authors hypothesised that their proliferation might be constitutively impaired in lung emphysema. Using explant cultures, lung fibroblasts were obtained from resected lungs of 10 patients with emphysema (median forced expiratory volume in one second (FEV1) 40% predicted) and 10 control patients (FEV1, 95% pred). The doubling time (DT) was measured over 4 days under standard conditions (10% foetal calf serum) prior and after cryopreservation. Additionally, in seven samples per group the total population doubling level (PDL) was determined. In emphysema, mean+/-sem DT was 33.6+/-2.8 h compared with 24.8+/-1.4 h in controls. The differences in DT were preserved after cryopreservation. Groups also differed in the initial slope of the PDL plot during long-term culture (up to 35 days). However, the median (range) maximum PDL did not differ significantly between groups (13.8 (7.4-22.6) versus 20.2 (11.2-25.5)). The current authors, therefore, suggest that the reduced proliferation rate in vitro of lung fibroblasts from patients with emphysema reflects a persistent, intrinsic failure of cellular replacement and maintenance in this disease, possibly in relation to pre-term aging.

摘要

肺气肿的特征是肺泡结构丧失,这在弹性回缩和气体交换中有所体现。由于成纤维细胞在维持结构方面起着关键作用,因此本文作者推测,在肺气肿患者中,成纤维细胞的增殖可能受到持续性损害。通过外植体培养,从10例肺气肿患者(一秒用力呼气量(FEV1)中位数为预测值的40%)和10例对照患者(FEV1为预测值的95%)切除的肺组织中获取肺成纤维细胞。在标准条件(10%胎牛血清)下,于冻存前后4天测量倍增时间(DT)。此外,每组选取7个样本测定总群体倍增水平(PDL)。肺气肿患者的平均±标准误DT为33.6±2.8小时,而对照组为24.8±1.4小时。冻存后DT的差异依然存在。在长期培养(长达35天)期间,两组在PDL曲线的初始斜率上也存在差异。然而,两组的最大PDL中位数(范围)无显著差异(13.8(7.4 - 22.6)对20.2(11.2 - 25.5))。因此,本文作者认为,肺气肿患者肺成纤维细胞体外增殖率降低反映了该疾病中细胞替代和维持的持续性内在缺陷,可能与过早衰老有关。

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