Modulation of digital flexor tendon healing by vascular endothelial growth factor gene transfection in a chicken model
Modulation of digital flexor tendon healing by vascular endothelial growth factor gene transfection in a chicken model
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血管内皮生长因子基因转染对鸡模型指屈肌腱愈合的调节
DOI：
10.1038/gt.2017.12
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发表时间：
2017-04-01
期刊：
影响因子：
5.1
通讯作者：
Tang, J. B.
中科院分区：
文献类型：
--
作者：
Mao, W. F.;Wu, Y. F.;Tang, J. B.
肌腱损伤的一个主要挑战是肌腱的内在愈合能力弱，可能导致手术后修复断裂。生长因子被认为是肌腱愈合过程中的关键。本研究旨在探讨腺相关病毒（AAV）载体介导的血管内皮生长因子（VEGF）基因对鸡肌腱愈合和分子事件的影响。将鸡长趾中的总共128个深屈肌腱完全横切，并在手术修复之前注射2 × 109个AAV 2-VEGF颗粒或盐水。分别于术后4、6、8周记录肌腱滑动距离，并对修复部位周围粘连情况进行评分。在2、4、6和8周时，测试愈合肌腱的极限强度。末端脱氧核苷酸转移酶dUTP缺口末端标记法检测肌腱组织细胞凋亡，免疫荧光法检测肌腱组织中Ⅲ型胶原和基质金属蛋白酶2（MMP 2）的表达。AAV 2-VEGF处理的肌腱和对照肌腱之间的滑动偏移和粘连评分相似。术后4周、6周和8周，AAV 2-VEGF的递送显着增加了愈合肌腱的极限强度（P < 0.05）。术后2 ~ 8周，肌腱核心区或表面区的细胞凋亡反应受到抑制。AAV 2-VEGF转染后第2、4、6、8周，III型胶原表达增强，MMP 2表达增强。本研究证实了AAV 2-VEGF在改善肌腱愈合强度而不加重肌腱损伤后粘连形成方面的治疗效果，为分子治疗在调节肌腱愈合中的应用提供了线索。
A major challenge in tendon injury is the weak intrinsic healing capacity of tendon that may cause rupture of the repair after surgery. Growth factors are believed to be critical during tendon healing. This study aimed to investigate the effects of vascular endothelial growth factor (VEGF) genes delivered by adeno-associated virus (AAV) vectors on tendon healing and molecular events involved in a chicken model. A total of 128 deep flexor tendons in the long toes of chickens were completely transected and injected with 2 x 10(9) particles of AAV2-VEGF or saline before surgically repaired. At postoperative 4, 6 and 8 weeks, the gliding excursions of tendon were recorded and adhesions around the repair site scored. At 2, 4, 6 and 8 weeks, the ultimate strengths of the healing tendons were tested. Terminal deoxynucleotide transferase dUTP nick end labeling assay were performed to detect cellular apoptosis and immunofluorescence staining to detect type III collagen and matrix metalloprotease-2 (MMP2) expression in tendon tissues. The gliding excursion and adhesion score were similar between AAV2-VEGF-treated tendons and the control tendons. Delivery of AAV2-VEGF significantly increased ultimate strength of the healing tendons at postoperative 4, 6 and 8 weeks (P < 0.05). Apoptotic reaction was inhibited from postoperative 2 to 8 weeks in tendon core area or surface area. Type III collagen expression was enhanced at 2, 4, 6 and 8 weeks and MMP2 expression enhanced at 2 and 4 weeks after AAV2-VEGF transfection. The current study confirms the therapeutic efficacy of AAV2-VEGF in improving healing strength of tendon without aggravating adhesion formation after tendon injury, shedding light on the application of molecular therapy in modulating tendon healing.