Quattrini Cristian, Jeziorska Maria, Boulton Andrew J M, Malik Rayaz A
Division of Cardiovascular Medicine, University of Manchester and Manchester Diabetes Centre, Manchester Royal Infirmary, Manchester, UK.
Diabetes Care. 2008 Jan;31(1):140-5. doi: 10.2337/dc07-1556. Epub 2007 Oct 12.
To assess the relevance of vascular endothelial growth factor (VEGF) in the maintenance of peripheral nerve integrity in diabetic neuropathy we have assessed the expression of VEGF and intra-epidermal nerve fiber density (IENFD) in skin biopsy samples from diabetic patients.
Fifty-three diabetic patients and 12 nondiabetic control subjects underwent neurological evaluation, electrophysiology, quantitative sensory, and autonomic function testing. Dermal blood flow responses were evaluated with laser Doppler flowmetry. Skin biopsies were performed on the dorsum of the foot, and IENFD was quantified and compared with the expression of vascular endothelial growth factor A (VEGF-A), its receptor vascular endothelial growth factor receptor 2 (VEGFR-2), hypoxia-inducible factor 1alpha (HIF-1alpha), and microvessel density.
IENFD decreased progressively with increasing severity of diabetic neuropathy (P < 0.001). The dermal blood flow response to acetylcholine was reduced in diabetic patients with mild and moderate neuropathy (P < 0.01), and the intensity of staining for epidermal VEGF-A was significantly reduced in diabetic patients compared with control subjects (P < 0.01). Epidermal HIF-1alpha and VEGFR-2 expression did not differ between groups.
Progressive endothelial dysfunction, a reduction in VEGF expression, and loss of intra-epidermal nerve fibers occurs in the foot skin of diabetic patients with increasing neuropathic severity.
为评估血管内皮生长因子（VEGF）在维持糖尿病性神经病变中周围神经完整性方面的相关性，我们评估了糖尿病患者皮肤活检样本中VEGF的表达及表皮内神经纤维密度（IENFD）。
53例糖尿病患者和12例非糖尿病对照者接受了神经学评估、电生理学、定量感觉及自主神经功能测试。用激光多普勒血流仪评估皮肤血流反应。在足背进行皮肤活检，对IENFD进行定量，并与血管内皮生长因子A（VEGF-A）、其受体血管内皮生长因子受体2（VEGFR-2）、缺氧诱导因子1α（HIF-1α）的表达及微血管密度进行比较。
IENFD随着糖尿病性神经病变严重程度的增加而逐渐降低（P<0.001）。轻度和中度神经病变的糖尿病患者对乙酰胆碱的皮肤血流反应降低（P<0.01），与对照者相比，糖尿病患者表皮VEGF-A的染色强度显著降低（P<0.01）。各组间表皮HIF-1α和VEGFR-2的表达无差异。
在糖尿病性神经病变严重程度增加的患者足部皮肤中，出现进行性内皮功能障碍、VEGF表达降低及表皮内神经纤维缺失。
