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肺移植后闭塞性细支气管炎综合征中促纤维化介质的基因表达

Gene expression of profibrotic mediators in bronchiolitis obliterans syndrome after lung transplantation.

作者信息

Bergmann M, Tiroke A, Schäfer H, Barth J, Haverich A

机构信息

Department of Internal Medicine, University of Kiel, Germany.

出版信息

Scand Cardiovasc J. 1998;32(2):97-103. doi: 10.1080/14017439850140247.

Abstract

Bronchiolitis obliterans syndrome (BOS) develops in one-third of lung transplant recipients. A fibroproliferative process involving mesenchymal cells is observed histopathologically. In order further to evaluate the pathomechanisms of BOS, the gene expression of platelet-derived growth factor (PDGF)-B and transforming growth factor (TGF)-beta 1 in bronchoalveolar lavage (BAL) cells of six lung transplant recipients and appropriate controls was studied. Equal amounts of total RNA were submitted to semiquantitative reverse transcription/polymerase chain reaction (RT-PCR), amplifying actin, PDGF-B and TGF-beta 1 using established protocols and primer sets. The signal/actin ratio was calculated based on laser densitometry measurements. TGF-beta 1 transcripts were detected in all samples, and a slight increase in BOS patients was observed. PDGF-B mRNA was increased in BAL samples from BOS patients compared to unaffected recipients and controls. Plotting the FEV1 in percent of vital capacity and the PDGF expression in BOS patients revealed an increased PDGF signal preceding lung function deterioration. The data were consistent with the hypothesis based mainly on in vitro findings that PDGF and TGF-beta contribute to the development of BOS.

摘要

闭塞性细支气管炎综合征(BOS)在三分之一的肺移植受者中出现。组织病理学观察到一个涉及间充质细胞的纤维增生过程。为了进一步评估BOS的发病机制,研究了6例肺移植受者及适当对照的支气管肺泡灌洗(BAL)细胞中血小板衍生生长因子(PDGF)-B和转化生长因子(TGF)-β1的基因表达。将等量的总RNA进行半定量逆转录/聚合酶链反应(RT-PCR),使用既定方案和引物对扩增肌动蛋白、PDGF-B和TGF-β1。基于激光密度测定法测量计算信号/肌动蛋白比率。在所有样本中均检测到TGF-β1转录本,且观察到BOS患者有轻微增加。与未受影响的受者及对照相比,BOS患者BAL样本中的PDGF-B mRNA增加。绘制BOS患者中以肺活量百分比表示的第一秒用力呼气容积(FEV1)和PDGF表达情况,结果显示在肺功能恶化之前PDGF信号增加。这些数据与主要基于体外研究结果的假说一致,即PDGF和TGF-β促成了BOS的发展。

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