既往研究表明，体表微生物区维持着皮肤完整性。糖尿病患者皮肤微生物区改变与溃疡相关，且其造成的细菌负载影响愈合。但目前糖尿病皮肤微生物区改变的分子机制不甚清楚。我们既往研究显示，长期糖尿病状态引起皮肤交感神经损害，从而造成皮肤排汗、表皮层厚度和皮肤内附件的改变。我们推测，糖尿病交感神经功能受损后通过影响角质形成细胞、皮脂腺和汗腺分泌抗菌肽、脂质，以及皮肤湿润度，最终致皮肤表面微生物区改变，同时皮肤免疫功能变化，成为糖尿病溃疡发生和难愈的关键因素。本课题通过对糖尿病不同患病时间皮肤表面微生物区的调查，了解其变化特点；建立失糖尿病交感神经动物模型，观察失神经后角质形成细胞抗菌肽分泌情况，以及汗液、脂质分泌特点。获取交感神经受损-微生物区变化-皮肤屏障功能破坏-糖尿病皮肤溃疡发生，且愈合期出现障碍的链条式证据。课题将为延缓糖尿病溃疡发生并加速难愈创面愈合提供新思路与手段，极大丰富组织修复理论。

Previous studies showed that skin microbiota maintains skin integrity. The change of microbiota is associated with the diabetic ulcers, and the bacterial load is too heavy to impact wound healing. However, the molecular mechanism of microbiota change in diabetic skin is still unclear.Our previous studies have shown that long-term diabetic state caused damage to sympathetic nerve in skin, and the damage of sympathetic nerve would affect skin perspiration, thickness and blood flow. We speculate that diabetes impaired the function of sympathetic nerve would affect the feature of keratinocytes, skin moisture, both lipids and antimicrobial peptides, which is secreted by sebaceous glands and sweat glands. Eventually, causing the changes of skin surface microbiota and immune function, which are the key factors in the occurrence of diabetic ulcer and hard-to-heal. The study investigate the skin surface microbiota in the different time of diabetes states to understand the change characteristics of microbiota; establish diabetes with sympathetic neurophy animal model to observe the affection of the antimicrobial peptides which is secreted by keratinocytes, and the secreted features of sweat and lipids in the denervated skin. Being sympathetic damaged induced change of microbiota and local immunity, skin barrier dysfunction, then caused diabetic skin ulcers, and healing disorders. The project would help to provide effective means to avoid diabetic wound, and accelerate the refractory wound healing. It would enrich the theory of wound healing.