In situ eNOS/NO up-regulation-a simple and effective therapeutic strategy for diabetic skin ulcer.
In situ eNOS/NO up-regulation-a simple and effective therapeutic strategy for diabetic skin ulcer.
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DOI：
10.1038/srep30326
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发表时间：
2016-07-25
影响因子：
4.6
通讯作者：
Fang Z
中科院分区：
文献类型：
--
作者：
Yang Y;Yin D;Wang F;Hou Z;Fang Z
糖尿病中一氧化氮（NO）合成减少和NO消耗增加导致组织血流量不足，这是糖尿病皮肤溃疡的发病机制和难治性的主要原因。本研究为糖尿病皮肤溃疡的治疗提供了一种简单有效的治疗策略--应用他汀类药物组织工程支架（TES）原位上调内皮型一氧化氮合酶（eNOS）的表达和NO的合成。体外人脐静脉内皮细胞实验表明，他汀负载TES缓解高糖诱导的细胞活力下降，并促进NO合成在高糖条件下。在大鼠糖尿病模型中，他汀类负载TES促进了再生组织中/周围的eNOS表达和NO合成。随后，观察到血管化加速和血液供应增加，随后伤口快速愈合。这些发现表明，原位上调eNOS/NO的他汀负载TES可能是一个有用的治疗方法，难治性糖尿病皮肤伤口。
Decreased nitric oxide (NO) synthesis and increased NO consumption in diabetes induces the inadequate blood flow to tissues that is primarily responsible for the pathogenesis and refractoriness of diabetic skin ulcers. The present study proposed a simple and effective therapeutic strategy for diabetic skin ulcers—in situ up-regulation of endothelial nitric oxide synthase (eNOS) expression and NO synthesis by statin-loaded tissue engineering scaffold (TES). In vitro experiments on human umbilical vein endothelial cells indicated that the statin-loaded TES relieved the high-glucose induced decrease in cell viability and promoted NO synthesis under high-glucose conditions. In a rat model of diabetes, the statin-loaded TES promoted eNOS expression and NO synthesis in/around the regenerated tissues. Subsequently, accelerated vascularization and elevated blood supply were observed, followed by rapid wound healing. These findings suggest that the in situ up-regulation of eNOS/NO by a statin-loaded TES may be a useful therapeutic method for intractable diabetic skin wounds.