Erlangen, Germany From the Department of Plastic and Hand Surgery and the Department of Experimental Medicine I, Nikolaus-Fiebiger Center of Molecular Medicine, Friedrich-Alexander-University of Erlangen-Nürnberg, University Hospital.
Plast Reconstr Surg. 2011 Jun;127(6):2293-2300. doi: 10.1097/PRS.0b013e318213a01f.
The aim of this study was to analyze the expression of hypoxia-inducible factor (HIF)-1α during ischemia and after reperfusion in muscle tissue in the context of microsurgical free muscle tissue transfer.
Ten patients with soft-tissue defects needing coverage with microsurgical free muscle flaps were included in this study. In all patients, the muscle samples were taken from free myocutaneous flaps. The first sample was taken before induction of ischemia in normoxia, another one was taken after 72 ± 11 minutes of ischemia, and the last one was taken 77 ± 22 minutes after reperfusion. The samples were analyzed using DNA microarray, real-time polymerase chain reaction, and immunohistochemistry.
DNA microarray, real-time polymerase chain reaction, and immunohistochemistry did not provide evidence of differential expression of HIF-1α comparing ischemia and reperfusion to normoxia. However, DNA microarray showed an up-regulation of activating transcription factor-3 during ischemia and spermine N1-acetyltransferase-1 during ischemia and reperfusion.
This study shows that ischemia and reperfusion induce alterations on the gene expression level in human muscle free flaps. Data from this study indicate that the expression of HIF-1α might not be affected but that other putative pathways of ischemic regulation might be of great interest. Finally, these findings correspond with the surgeon's clinical experience that the accepted times of ischemia, generally up to 90 minutes, are not sufficient to induce pathophysiologic processes, which can ultimately lead to flap loss.
本研究旨在分析在微血管游离组织移植中,缺血及再灌注时肌肉组织中缺氧诱导因子(HIF)-1α的表达。
本研究纳入 10 例因软组织缺损需要接受游离肌皮瓣覆盖的患者。所有患者均取自体游离肌皮瓣组织样本。在正常氧供条件下,于缺血前、缺血 72±11 分钟后和再灌注 77±22 分钟后分别取一组样本。采用 DNA 微阵列、实时聚合酶链反应和免疫组织化学方法分析样本。
DNA 微阵列、实时聚合酶链反应和免疫组织化学结果均未显示缺血及再灌注与正常氧供相比 HIF-1α的表达有差异。然而,DNA 微阵列显示在缺血期间激活转录因子-3 上调,在缺血及再灌注期间精脒 N1-乙酰转移酶-1 上调。
本研究表明缺血及再灌注会引起游离肌皮瓣的基因表达水平发生改变。本研究的数据表明 HIF-1α的表达可能不受影响,但其他潜在的缺血调节途径可能具有重要意义。最后,这些发现与外科医生的临床经验一致,即公认的缺血时间(一般不超过 90 分钟)不足以引发病理生理过程,最终导致皮瓣坏死。