摘要
目的研究糖尿病大鼠皮肤组织中表皮细胞的增殖改变及其可能机制。方法12只SPF级SD大鼠随机分为糖尿病组(6只)和正常对照组(6只),糖尿病大鼠以STZ诱导。成模后8周,二组同时采集背部皮肤,观察表皮的组织学特征;流式细胞术检测表皮细胞的细胞周期;Westernblot检测细胞增殖调节因子cyclinD1、cyclinB1和cdk4的表达水平,并测定表皮细胞丝裂期促进因子(MPF)的组蛋白激酶活性。结果与正常组相比,糖尿病大鼠表皮结构欠清晰,部分表皮缺乏复层排列,表皮细胞数量明显减少,表皮层厚度明显变薄;S期和G2/M期表皮细胞百分比均显著降低(P<0.01,P<0.05);糖尿病组cdk4的表达水平显著低于正常组(P<0.05),两组间cyclinD1、cyclinB1表达无显著差异(P>0.05);糖尿病组表皮细胞MPF活性显著降低(P<0.01)。结论糖尿病大鼠皮肤表皮细胞处于明显增殖抑制状态,这种增殖抑制可能与cdk4的低表达和MPF活性下降有关。
Objective To investigate the proliferative events of keratinocytes and possible mechanisms in the diabetic skin. Methods Twelve Sprague-Dawley rats were randomized into control group (n=6) and STZ-induced diabetic group (n=6). The shaved skin specimens from the back of rats were collected at 8 weeks post STZ-induction. The epidermal histological characteristics were observed. The cell cycles of keratinocytes were determined by flow cytometry. The expression of cyclin D1, cyclin B1 and cdk4 in keratinocytes was detected by Western blot analy- sis. The histone H1 kinase activity of MPF was measured. Results The thickness of the epidermis layer was reduced obviously in the diabetic skin, with the morphological characteristics of the obscure multilayer epithelium features. In the diabetic skin, the percentages of S stage and G 2/M stages of keratinocytes were obviously decreased. Dowm-regulated cdk4 was observed in diabetic group. There were no dramatic variations for expressions of cyclin D1 and cyclin B1 between diabetic and normal groups. The histone H1 kinase activity of MPF reduced markedly in diabetes. Conclusion There is a marked inhibition of proliferation for keratinocytes in the diabetic skin due to dowm-regulated cdk4 and histone H1 kinase activity of MPF.
出处
《上海第二医科大学学报》
CSCD
北大核心
2005年第6期541-544,共4页
Acta Universitatis Medicinalis Secondae Shanghai
基金
国家重点基础研究规划项目(973项目)(G1999054205)资助.
