Electroporatic delivery of TGF-β1 gene works synergistically with electric therapy to enhance diabetic wound healing in db/db mice
Electroporatic delivery of TGF-β1 gene works synergistically with electric therapy to enhance diabetic wound healing in db/db mice
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DOI：
10.1111/j.0022-202x.2004.23309.x
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发表时间：
2004-10-01
影响因子：
6.5
通讯作者：
Huang, L
中科院分区：
文献类型：
--
作者：
Lee, PY;Chesnoy, S;Huang, L
电刺激（ES）是用于伤口愈合的治疗性处理。电穿孔是一种ES，是一种成熟的基因递送方法。我们假设，可以找到适当的条件下，电和基因疗法可以添加应用于治疗糖尿病伤口愈合。为了研究转化生长因子β 1（TGF-β 1）在局部的表达和治疗效果，采用db/db小鼠全层切创模型，检测伤后24 h TGF-β 1细胞因子水平，并对创面进行组织学检查。此外，通过每天测量伤口面积来评估伤口闭合，持续14 d。我们发现，注射器电极比传统的卡尺电极更有效。此外，糖尿病皮肤比正常皮肤对电穿孔损伤更敏感。糖尿病皮肤的最佳电刺激条件为6个100 V/cm脉冲，20 ms，在此条件下，电治疗伤口的愈合速度明显加快。此外，当TGF-β 1基因通过电脉冲传递时，愈合率进一步提高。皮内注射质粒TGF-β 1后5 - 7天，然后进行电穿孔，伤口床显示上皮再生率、胶原合成和血管生成增加。这些数据表明，在遗传性糖尿病模型中，电效应和基因效应确实协同作用。
Electrical stimulation (ES) is a therapeutic treatment for wound healing. Electroporation, a type of ES, is a well-established method for gene delivery. We hypothesize that proper conditions can be found with which both electrical and gene therapies can be additively applied to treat diabetic wound healing. For the studies of transforming growth factor-beta1 (TGF-beta1) local expression and therapeutic effects, full thickness excisional wound model of db/db mice was used, we measured TGF-beta1 cytokine level at 24 h postwounding and examined wounds histologically. Furthermore, wound closure was evaluated by wound-area measurements at each day for 14 d. We found that syringe electrodes are more effective than the conventional caliper electrodes. Furthermore, diabetic skin was more sensitive to the electroporative damage than the normal skin. The optimal condition for diabetic skin was six pulses of 100 V per cm for 20 ms. Under such condition, the healing rate of electrically treated wound was significantly accelerated. Furthermore, when TGF-beta1 gene was delivered by electric pulses, the healing rate was further enhanced. Five to seven days postapplication of intradermal injection of plasmid TGF-beta1 followed by electroporation, the wound bed showed an increased reepithelialization rate, collagen synthesis, and angiogenesis. The data indicates that indeed the electric effect and gene effect work synergistic in the genetically diabetic model.