Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Am J Pathol. 2011 May;178(5):2215-23. doi: 10.1016/j.ajpath.2011.01.015.
Diabetic skin is known to have deficient wound healing properties, but little is known of its intrinsic biomechanical properties. We hypothesize that diabetic skin possesses inferior biomechanical properties at baseline, rendering it more prone to injury. Skin from diabetic and nondiabetic mice and humans underwent biomechanical testing. Real-time PCR was performed for genes integral to collagen synthesis and degradation. MMP-2 and MMP-9, and TIMP-1 protein levels were assessed by ELISA and zymography. Collagen I and III content was assessed using Western blot analysis. At baseline, both murine and human diabetic skin was biomechanically inferior compared to nondiabetic skin, with decreased maximum stress and decreased modulus (P < 0.001 and < 0.05, respectively). Surprisingly, the expression of genes involved in collagen synthesis were significantly up-regulated, and genes involved in collagen degradation were significantly down-regulated in murine diabetic skin (P < 0.01). In addition, MMP-2 and MMP-9/TIMP-1 protein ratios were significantly lower in murine diabetic skin (P < 0.05). Collagen I levels and I:III ratios were lower in diabetic skin (P < 0.05). These findings suggest that the predisposition of diabetics to wounds may be the result of impaired tissue integrity at baseline, and are due, in part, to a defect in the regulation of collagen protein synthesis at the post-transcriptional level.
糖尿病患者的皮肤伤口愈合能力较差，但人们对其内在的生物力学特性知之甚少。我们假设糖尿病患者的皮肤在基线时就具有较差的生物力学特性，使其更容易受伤。对糖尿病和非糖尿病小鼠和人类的皮肤进行了生物力学测试。实时 PCR 用于评估与胶原蛋白合成和降解相关的基因。通过 ELISA 和酶谱法评估 MMP-2 和 MMP-9 以及 TIMP-1 蛋白水平。使用 Western blot 分析评估胶原蛋白 I 和 III 的含量。在基线时，与非糖尿病皮肤相比，无论是在小鼠还是人类的糖尿病皮肤中，最大应力和模量均明显降低（P<0.001 和 <0.05）。令人惊讶的是，在糖尿病小鼠皮肤中，参与胶原蛋白合成的基因表达显著上调，而参与胶原蛋白降解的基因表达显著下调（P<0.01）。此外，糖尿病小鼠皮肤中的 MMP-2 和 MMP-9/TIMP-1 蛋白比率明显较低（P<0.05）。糖尿病皮肤中的胶原蛋白 I 水平和 I:III 比值较低（P<0.05）。这些发现表明，糖尿病患者易发生伤口的倾向可能是由于基线时组织完整性受损所致，部分原因是由于转录后水平胶原蛋白蛋白合成的调节缺陷。
