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原位内皮型一氧化氮合酶/一氧化氮上调——一种治疗糖尿病皮肤溃疡的简单有效策略。

In situ eNOS/NO up-regulation-a simple and effective therapeutic strategy for diabetic skin ulcer.

作者信息

Yang Ye, Yin Dengke, Wang Fei, Hou Ziyan, Fang Zhaohui

机构信息

School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.

Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei 230031, China.

出版信息

Sci Rep. 2016 Jul 25;6:30326. doi: 10.1038/srep30326.

DOI:10.1038/srep30326
PMID:27453476
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4958962/
Abstract

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.

摘要

糖尿病中一氧化氮（NO）合成减少和NO消耗增加会导致组织血流不足，这是糖尿病皮肤溃疡发病机制和难治性的主要原因。本研究提出了一种针对糖尿病皮肤溃疡的简单有效的治疗策略——通过载有他汀类药物的组织工程支架（TES）原位上调内皮型一氧化氮合酶（eNOS）表达和NO合成。对人脐静脉内皮细胞的体外实验表明，载有他汀类药物的TES缓解了高糖诱导的细胞活力下降，并在高糖条件下促进了NO合成。在糖尿病大鼠模型中，载有他汀类药物的TES促进了再生组织内/周围的eNOS表达和NO合成。随后，观察到血管生成加速和血液供应增加，接着伤口迅速愈合。这些发现表明，载有他汀类药物的TES原位上调eNOS/NO可能是治疗顽固性糖尿病皮肤伤口的一种有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/1f7791ce6230/srep30326-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/62706a1f4f29/srep30326-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/65005285c8c7/srep30326-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/8a2fb114d03d/srep30326-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/f918ac39a306/srep30326-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/a8375fc0c064/srep30326-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/2f643ef1d07c/srep30326-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/1f7791ce6230/srep30326-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/62706a1f4f29/srep30326-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/65005285c8c7/srep30326-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/8a2fb114d03d/srep30326-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/f918ac39a306/srep30326-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/a8375fc0c064/srep30326-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/2f643ef1d07c/srep30326-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d52/4958962/1f7791ce6230/srep30326-f7.jpg

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