糖尿病大鼠皮肤组织β-连环素与增殖细胞核抗原的特征及意义

Expressions and significances of beta-catenin and proliferating cell nuclear antigen in skin tissues of rats with diabetic mellitus

目的:观察糖尿病SD大鼠皮肤与正常大鼠皮肤组织表皮β-连环素(β-catenin)、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、角蛋白19(keratin19,K19)和β1整合素的表达差异,探讨其在糖尿病皮肤难愈创面修复中的意义。方法:20只SD大鼠随机分为DM组和正常对照组。DM组大鼠采用一次性腹腔注射链脲佐菌素65mg/kg制备糖尿病大鼠模型,成模第4周取大鼠背部全层皮肤,并取正常皮肤标本作为对照,行HE染色及β-catenin、PCNA、K19和β1整合素免疫组织化学染色,图像分析软件测量表皮厚度及阳性细胞积分光密度平均值。结果:DM组皮肤组织表皮β-catenin、PCNA、K19和β1整合素的表达均显著低于正常对照组皮肤(P<0.01)。DM组与正常对照组大鼠的表皮厚度[(12.45±1.46)μm vs(22.9±2.28)μm,P<0.01]及皮肤中β-catenin(169.78±37.29vs217.88±23.51,P<0.01)、PCNA(143.17±19.82vs175.05±20.84,P<0.01)、K19(139.54±20.69vs168.96±17.97,P<0.01)和β1整合素(150.58±19.98vs181.79±15.94,P<0.01)的阳性细胞积分光密度平均值相比差异有统计学意义。结论:糖尿病大鼠皮肤组织表皮β-catenin、PCNA表达均较正常皮肤明显减少,可能是导致糖尿病表皮干细胞数量减少、活性降低且创面难愈的重要机制之一。

Objective To observe the expressions of β-catenin, proliferating cell nuclear antigen （PCNA）, keratinl9 （K19） and β1-integrin in skin tissues of normal SD rats and rats with diabetic mellitus （DM）, then to study their correlations with difficuh recovering wounds of diabetic skin. Methods 20 SD rats were divided into DM group and control group randomly. The DM rat models were induced by intraperitoneal injection of 65 mg/kg of streptozocin （STZ）, then full-thickness skins were taken from the back of diabetic rats at the 4th week of modeling. And normal skin samples were taken as controls. Hematoxylin and eosin （HE） staining and immunohistochemical staining were used to detect β-catenin, PCNA, K19 and β1-integrin. Then the epidermal thickness and the average integral optical density of positive cells of basal layer were measured with image analysis software. Results The expressions of β-catenin, PCNA, K19, and β1-integrin were significantly lower in DM group than those in control group （P 〈 0.01 ）. There were significant differences in the epidermal thickness and the average integral optical density of the positive cells of β-catenin, PCNA, K19, and β1-integrin between DM group and control group [ （12.45 ± 1,46） μmvs （22.9±2.28） μm, P〈0.01; 169.78±37.29vs 217.88±23.51, P〈0.01; 143.17± 19.82vs 175.05 ± 20.84, P 〈 0.01 ; 139.54 ± 20.69 vs 168.96 ± 17.97,P 〈 0.01 ; 150.58 ± 19.98 vs 181.79 ± 15.94, P 〈 0.01 ; respectively ]. Conclusion The expressions of of β-eatenin and PCNA in skin tissues of rats with diabetic mellitus were significantly decreased, which may be one of the important mechanisms that reduced epidermic stem ceils and its activity and that was related to difl＇icult recovering wounds of DM.