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血管内皮生长因子(VEGF)基因转染后大鼠缺血性皮瓣和肌皮瓣存活情况改善

Improved survival of rat ischemic cutaneous and musculocutaneous flaps after VEGF gene transfer.

作者信息

Antonini Andrea, Zacchigna Serena, Papa Giovanni, Novati Federico, Pascone Michele, Giacca Mauro

机构信息

Plastic Surgery Unit, Faculty of Medicine and Surgery, University of Trieste, Italy.

出版信息

Microsurgery. 2007;27(5):439-45. doi: 10.1002/micr.20378.

DOI:10.1002/micr.20378
PMID:17596844
Abstract

When harvesting microsurgical flaps, the main goals are to obtain as much tissue as possible based on a single vascular pedicle and a reliable vascularization of the entire flap. These aims being in contrast to each other, microsurgeons have been looking for an effective way to enhance skin and muscle perfusion in order to avoid partial flap loss in reconstructive surgery. In this study we demonstrate the efficacy of VEGF 165 delivered by an Adeno-Associated Virus (AAV) vector in two widely recognized rat flap models. In the rectus abdominis myocutaneous flap, intramuscular injection of AAV-VEGF reduced flap necrosis by 50%, while cutaneous delivery of the same amount of vector put down the epigastric flap's ischemia by >40%. Histological evidence of neoangiogenesis (enhanced presence of CD31-positive capillaries and alpha-Smooth Muscle Actin-positive arteriolae) confirmed the therapeutic effect of AAV-VEGF on flap perfusion.

摘要

在切取显微外科皮瓣时,主要目标是基于单一血管蒂获取尽可能多的组织,并确保整个皮瓣有可靠的血管化。由于这些目标相互矛盾,显微外科医生一直在寻找一种有效的方法来增强皮肤和肌肉灌注,以避免重建手术中皮瓣部分坏死。在本研究中,我们在两种广泛认可的大鼠皮瓣模型中证明了腺相关病毒(AAV)载体递送的VEGF 165的有效性。在腹直肌肌皮瓣中,肌肉内注射AAV-VEGF可使皮瓣坏死减少50%,而相同剂量载体的皮肤递送可使腹壁皮瓣的缺血减少>40%。新生血管形成的组织学证据(CD31阳性毛细血管和α-平滑肌肌动蛋白阳性小动脉的存在增加)证实了AAV-VEGF对皮瓣灌注的治疗效果。

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1
Improved survival of rat ischemic cutaneous and musculocutaneous flaps after VEGF gene transfer.血管内皮生长因子(VEGF)基因转染后大鼠缺血性皮瓣和肌皮瓣存活情况改善
Microsurgery. 2007;27(5):439-45. doi: 10.1002/micr.20378.
2
Improved survival of ischemic cutaneous and musculocutaneous flaps after vascular endothelial growth factor gene transfer using adeno-associated virus vectors.使用腺相关病毒载体进行血管内皮生长因子基因转移后,缺血性皮肤和肌皮瓣的存活率提高。
Am J Pathol. 2005 Oct;167(4):981-91. doi: 10.1016/S0002-9440(10)61188-1.
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Enhancement of flap survival and changes in angiogenic gene expression after AAV2-mediated VEGF gene transfer to rat ischemic flaps.腺相关病毒 2 介导血管内皮生长因子基因转染对大鼠缺血皮瓣存活的影响及血管生成基因表达的变化。
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Delivery of FGF-2 but not VEGF by encapsulated genetically engineered myoblasts improves survival and vascularization in a model of acute skin flap ischemia.在急性皮瓣缺血模型中,通过封装的基因工程成肌细胞递送成纤维细胞生长因子-2(FGF-2)而非血管内皮生长因子(VEGF)可提高存活率并促进血管形成。
Gene Ther. 2001 Apr;8(7):523-33. doi: 10.1038/sj.gt.3301436.
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Comparison of the effectiveness of gene therapy with transforming growth factor-beta or extracorporal shock wave therapy to reduce ischemic necrosis in an epigastric skin flap model in rats.在大鼠腹壁皮瓣模型中比较基因治疗联合转化生长因子-β与体外冲击波疗法减少缺血性坏死的有效性。
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Combination of VEGF(165)/Angiopoietin-1 gene and endothelial progenitor cells for therapeutic neovascularization.血管内皮生长因子(165)/血管生成素-1基因与内皮祖细胞联合用于治疗性血管新生
Eur J Pharmacol. 2007 Jul 30;568(1-3):222-30. doi: 10.1016/j.ejphar.2007.04.047. Epub 2007 May 10.
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Electroporation of vascular endothelial growth factor gene in a unipedicle transverse rectus abdominis myocutaneous flap reduces necrosis.血管内皮生长因子基因电穿孔转染单蒂腹直肌肌皮瓣可减少坏死。
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Comparison of the effectiveness of gene therapy with vascular endothelial growth factor or shock wave therapy to reduce ischaemic necrosis in an epigastric skin flap model in rats.在大鼠腹壁皮瓣模型中比较血管内皮生长因子基因治疗与冲击波治疗减少缺血性坏死的效果。
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[Angiogenesis VEGF165 gene therapy with AdVEGF- a new delay procedure for flaps].[腺病毒介导血管内皮生长因子165基因治疗促进皮瓣血管生成——一种新的皮瓣延迟方法]
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Adeno-associated virus vectors simultaneously encoding VEGF and angiopoietin-1 enhances neovascularization in ischemic rabbit hind-limbs.同时编码血管内皮生长因子和血管生成素-1的腺相关病毒载体可增强缺血兔后肢的新生血管形成。
Acta Pharmacol Sin. 2007 Apr;28(4):493-502. doi: 10.1111/j.1745-7254.2007.00527.x.

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Int J Mol Sci. 2024 Sep 25;25(19):10330. doi: 10.3390/ijms251910330.
2
VEGF and Other Gene Therapies Improve Flap Survival-A Systematic Review and Meta-Analysis of Preclinical Studies.血管内皮生长因子及其他基因疗法可改善皮瓣存活——一项临床前研究的系统评价与Meta分析
Int J Mol Sci. 2024 Feb 23;25(5):2622. doi: 10.3390/ijms25052622.
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Effect of hyperbaric oxygenation on random rat skin flaps vascularization.
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Acta Cir Bras. 2021 Nov 8;36(9):e360906. doi: 10.1590/ACB360906. eCollection 2021.
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The effect of atorvastatin on survival of rat ischemic flap.阿托伐他汀对大鼠缺血皮瓣存活的影响。
Kaohsiung J Med Sci. 2013 Apr;29(4):187-93. doi: 10.1016/j.kjms.2012.08.032. Epub 2012 Dec 20.
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Use of gene-modified keratinocytes and fibroblasts to enhance regeneration in a full skin defect.利用基因修饰的角质形成细胞和成纤维细胞增强全层皮肤缺损的再生。
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