糖尿病皮肤“隐性损害”的机制研究

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目的 明确糖尿病皮肤的伤前病理改变是创面难愈的潜在机制。 方法 体重2 0 0~ 2 2 0 g的SPF级SD大鼠 14只 ,分为糖尿病组 (8只 )和正常对照组 (6只 ) ,以链脲佐菌素(STZ)诱导糖尿病大鼠模型 ,成模后 8周与正常对照组同时采集背部皮肤 ,观察皮肤的组织学特征 ,检测表皮细胞周期 ,测定皮肤组织糖含量、糖基化终末产物 (AGEs)蓄积程度、羟脯氨酸含量、Ⅰ型和Ⅲ型胶原、碱性成纤维细胞生长因子 (bFGF)表达量及其被糖基化程度、髓过氧化物酶 (MPO)含量以及基质金属蛋白酶 - 2 (MMP - 2 )活性和基质金属蛋白酶抑制因子 - 2 (TIMP - 2 )水平。 结果 糖尿病皮肤表皮细胞层次欠清晰 ,部分表皮细胞缺乏复层排列 ,棘细胞数量明显减少 ,表皮层厚度明显变薄 ;糖尿病大鼠皮肤真皮层明显变薄 ,胶原纤细、排列紊乱 ,Ⅲ型胶原分泌增加 ,Ⅰ、Ⅲ胶原交织排列 ,部分胶原可见变性、肿胀 ,胶原变性区域可见慢性炎性细胞局灶性浸润 ;糖尿病大鼠皮肤组织糖含量明显高于正常对照组 ,AGEs明显蓄积 ;糖尿病大鼠皮肤S期以及G2 /M期的表皮细胞百分比明显低于正常对照组 ;糖尿病皮肤局部bFGF释放和表达虽不少于正常皮肤 ,但存在明显的bFGF糖基化 ;此外 ,糖尿病大鼠皮肤组织MPO含量明显增多、MMP - 2活性明显增加 ,活化的MMP - 2 Objective To clarify the pre-injury pathological changes of diabetic skin is a potential mechanism of refractory wounds. Methods Fourteen SPF SD rats weighing 200-220 g were divided into diabetic group (n = 8) and normal control group (n = 6), and streptozotocin (STZ) -induced diabetic rat model At 8 weeks after operation, the skin of the back was collected at the same time as the normal control group. The histological features of the skin were observed. The epidermal cell cycle was measured. The content of sugar in the skin tissue, the accumulation of advanced glycation end products (AGEs), hydroxyproline content , Type Ⅰ and type Ⅲ collagen, basic fibroblast growth factor (bFGF) and their degree of glycosylation, myeloperoxidase (MPO) and matrix metalloproteinase - 2 The level of matrix metalloproteinase inhibitor - 2 (TIMP - 2). Results The level of epidermal cells in diabetic skin was not clear. Some epidermal cells lacked arrangement of stratum, the number of spine cells decreased significantly, and the thickness of epidermis became thinner. The dermal layer of diabetic rats became thinner, with slender collagen and disordered collagen, Increased collagenase Ⅰ, Ⅲ collagen arrangement, partial collagen visible denaturation, swelling, collagen degeneration region visible chronic inflammatory cell focal infiltration; diabetic rat skin tissue sugar content was significantly higher than the normal control group, AGEs significant accumulation; diabetic rats Skin S phase and G2 / M epidermal cell percentage was significantly lower than the normal control group; local skin bFGF release and expression of diabetic skin, although not less than normal, but there is significant bFGF glycosylation; In addition, diabetic rat skin tissue MPO The contents of MMP - 2 and MMP - 2 were significantly increased, and the activated MMP - 2 was significantly increased
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