Krishnan Singhan T M, Quattrini Cristian, Jeziorska Maria, Malik Rayaz A, Rayman Gerry
Diabetes Centre, Ipswich Hospital, Ipswich, UK.
Diabetes Care. 2007 Dec;30(12):3058-62. doi: 10.2337/dc07-1421. Epub 2007 Sep 26.
Delayed wound healing in diabetic patients without large-vessel disease has been attributed to microvascular dysfunction, neuropathy, and abnormal cellular and inflammatory responses. The role of these abnormalities has mainly been examined in animal models. Few studies have been undertaken in diabetic patients, and those that have are limited due to analysis in wounds from chronic ulcers. In this study, we quantified the rate of wound healing in relation to skin neurovascular function and structure following a dorsal foot skin biopsy in type 2 diabetes.
Twelve healthy control subjects and 12 type 2 diabetic subjects with neuropathy but without macrovascular disease were studied. We quantified rate of wound healing and related it to skin microvascular function (laser Doppler imager LDI), blood vessel density, small nerve fiber function (LDI(flare)) and nerve fiber density, vascular endothelial growth factor (VEGF) and its receptor (FLK1), and hypoxia-inducible factor (HIF)-1alpha expression.
The rate of wound closure was identical between control subjects and diabetic patients despite a significant reduction in maximum hyperemia (LDI(max)), epidermal and dermal VEGF-A, and epidermal and dermal blood vessel VEGFR-2 expression as well as the neurogenic flare response (LDI(flare)) and dermal nerve fiber density. There was no significant difference in HIF-1alpha and dermal blood vessel density between control subjects and diabetic patients.
In conclusion, the results of this study suggest that wound closure in subjects with type 2 diabetes is not delayed despite significant alterations in neurovascular function and structure.
无大血管疾病的糖尿病患者伤口愈合延迟归因于微血管功能障碍、神经病变以及异常的细胞和炎症反应。这些异常情况的作用主要在动物模型中进行了研究。在糖尿病患者中开展的研究较少，且由于对慢性溃疡伤口的分析，这些研究存在局限性。在本研究中，我们对2型糖尿病患者进行足背皮肤活检后，量化了伤口愈合速率与皮肤神经血管功能和结构之间的关系。
研究了12名健康对照者和12名患有神经病变但无大血管疾病的2型糖尿病患者。我们量化了伤口愈合速率，并将其与皮肤微血管功能（激光多普勒成像仪LDI）、血管密度、小神经纤维功能（LDI(红晕)）和神经纤维密度、血管内皮生长因子（VEGF）及其受体（FLK1）以及缺氧诱导因子（HIF）-1α表达相关联。
尽管最大充血量（LDI(最大值)）、表皮和真皮VEGF-A、表皮和真皮血管VEGFR-2表达以及神经源性红晕反应（LDI(红晕)）和真皮神经纤维密度显著降低，但对照者和糖尿病患者的伤口闭合速率相同。对照者和糖尿病患者之间HIF-1α和真皮血管密度无显著差异。
总之，本研究结果表明，尽管神经血管功能和结构发生了显著改变，但2型糖尿病患者的伤口闭合并未延迟。
