胰岛素对糖尿病大鼠潜在皮肤病变防护作用的机理研究  

Amelioration of lantent skin lesions in streptozotocin-induced diabetic rats by insulin

作　　者：陈向芳[1] 林炜栋[1] 陆树良[2] 张立斌[1] 张慧[1] 刘志民[1] 

机构地区：[1]第二军医大学附属长征医院内分泌科,上海200003 [2]上海第二医科大学附属瑞金医院上海市烧伤研究所

出　　处：《中华医学杂志》2005年第45期3176-3180,共5页National Medical Journal of China

基　　金：国家973重点基础研究发展规划资助项目(G1999054205)

摘　　要：目的探讨胰岛素对糖尿病潜在皮肤病变保护作用的机理。方法用链脲佐菌素(STZ)将8周龄雄性SD大鼠诱导成速发型糖尿病大鼠模型,分为应用胰岛素强化控制血糖组(A组)(n=27)和未控制血糖组(B组)(n=27),并以正常大鼠作对照(C组)(n=27),分别于致病后4、8和12周获取大鼠背部中央的皮肤标本。应用HE染色,观察皮肤组织学的改变;应用Beckman′s生化自动分析仪检测皮肤组织匀浆的糖含量;采用F3010荧光分光光度计和免疫组织化学技术测定皮肤中晚期糖基化终末产物(AGE)含量的变化;应用透射电镜观察皮肤微血管超微结构的改变。结果组织学观察,致病后12周B组糖尿病大鼠皮肤明显变薄,表皮细胞层次欠清晰,部分表皮缺乏复层排列;真皮层部分胶原萎缩、肿胀,退化变性,并伴随程度不等的炎性细胞浸润;皮下脂肪进行性萎缩或消失。A组糖尿病大鼠皮肤未出现上述明显的组织学改变。B组糖尿病大鼠皮肤糖含量在各时相点均明显高于A组和C组(P<0.01),而A组与C组之间差异无统计学意义(P>0.05)。B组和A组糖尿病大鼠皮肤胶原提取液的荧光值均高于相应年龄正常大鼠,病程越长,荧光值增加越明显。8周和12周的B组糖尿病大鼠皮肤胶原提取液的荧光值明显高于同期A组的糖尿病大鼠;8周时B组为(34U/mg±4U/mg),A组为(29U/mg±3U/mg,P<0.05);12周时B组为(41U/mg±4U/mg),A组为(32U/mg±4U/mg,P<0.05)。免疫组织化学检查亦显示B组糖尿病大鼠皮肤中AGE表达阳性率于8周和12周均显著高于A组,8周时B组为32%±4%,A组为25%±5%,(P<0.05);12周时B组为39%±5%,A组为27%±4%,(P<0.05)。透射电镜观察A组糖尿病大鼠皮肤血管内皮细胞变性和基底膜增厚程度均明显好于B组。结论皮肤中AGE蓄积和高糖是糖尿病皮肤病变的重要致病因素之一,胰岛素对糖尿病大鼠潜在皮肤病变具有防护作用,其作用机制可能与严格控制血糖、抑制AGE的合成、�Objective To explore the lantent skin lesions in streptozotocin-induced diabetic rats and the mechanism of insulin prevention. Methods 81 male Sprague-Dawley （SD） rats were randomized into control （ C, n = 27 ） and STZ-induced diabetic groups （ n = 54 ）, and then the diabetic rats were randomized into 2 groups： Group A group （n = 27 ） that was treated with insulin enough to control the high concentration of blood glucose strictly, and Group B group （n = 27 ） in which insulin was given too nut not sufficient to control the high blood glucose. Twenty-seven normal rats were used as controls. Four, eight, and twelve weeks after STZ-induction, skin specimens from the back were collected to undergo hematoxylineosin staining and histological examination. The skin glucose content was measured by Beckman＇s autoanalyzer. The skin advanced glycation end products （AGEs） concentration was assessed by fluorescence spectrophotometry and immunohistochemistry. The uhrastructure changes of skin microvessel were observed by electron microscopy. Results Twelve weeks after the establishment of the DM model the skin thickness of Group B was decreased, the features of muhilayer epithelium structure disappeared in epidermis, and part of the collagen fibers in dermis became atrophic, swollen and degenerated, infiltration of inflammatory ceils to different degrees was found, and subcutaneous fat showed progressive atrophy or disappeared. However,such changes were not detected in Group A. The skin glucose contents of Group B at different time points were all higher than those of Group A and Group （ all P 〈 0.01 ） without a significant difference between Groups A and C. The fluorescence values of skin collagen extracts of Groups A and B were significantly higher than that of normal rats. The S-week fluorescence value of skin collagen extracts of Groups B was 34 U/mg ± 4 U/rag, significantly higher than that of Group A （29 U/mg ± 3 U/mg,P 〈 0.05 ） . The 12-week fluorescence value of skin collagen ext

关 键 词：胰岛素 糖尿病 糖基化终产物 高级 

分 类 号：R587.1[医药卫生—内分泌]