CAJ | 학술논문

目的探讨糖尿病(DM)状态对真皮成纤维细胞(FB)生物学行为的影响. 方法通过DM大鼠模型,对皮肤的组织生物学特征及真皮FB的生物学行为进行检测. 结果 (1)在DM状态下,皮肤出现一系列组织学改变(厚度明显变薄和炎性细胞浸润等)、皮肤糖含量与炎症介质水平及糖基化终末产物(AGEs)的表达异常升高、真皮FB的真皮增殖细胞核内抗原表达上升,但增殖周期显示处于S期细胞比例升高而G2/M期细胞却未相应增加.(2)在高糖和AGE-人血清白蛋白(HSA)干预下,真皮FB的生长抑制和凋亡细胞百分率显著高于正常对照(NC)组(P<0.05或0.01),且生长抑制和凋亡率呈AGE-HSA的剂量依赖性. 结论在DM状态下,高糖环境和AGEs蓄积是导致FB功能异常的重要原因,可能也是造成DM患者皮肤"隐性损害"以及创面难愈的重要原因之一.
목적탐토당뇨병(DM)상태대진피성섬유세포(FB)생물학행위적영향. 방법통과DM대서모형,대피부적조직생물학특정급진피FB적생물학행위진행검측. 결과 (1)재DM상태하,피부출현일계렬조직학개변(후도명현변박화염성세포침윤등)、피부당함량여염증개질수평급당기화종말산물(AGEs)적표체이상승고、진피FB적진피증식세포핵내항원표체상승,단증식주기현시처우S기세포비례승고이G2/M기세포각미상응증가.(2)재고당화AGE-인혈청백단백(HSA)간예하,진피FB적생장억제화조망세포백분솔현저고우정상대조(NC)조(P<0.05혹0.01),차생장억제화조망솔정AGE-HSA적제량의뢰성. 결론재DM상태하,고당배경화AGEs축적시도치FB공능이상적중요원인,가능야시조성DM환자피부"은성손해"이급창면난유적중요원인지일.
Objective To study the effects of high concentrations of glucose on biological behavior of dermal fibroblast in diabetic rats. Methods 12 Sprague-Dawley rats weighing 200~220 g were divided into control and STZ-induced diabetic groups. The shaved skin specimens from the back of rats were collected on 8w after hyperglycemia treatment. The cutaneous histological characteristics were observed. The local contents of glucose, AGEs and hydroxyproline(OHP), PCNA expression,the proliferation and apoptosis of dermal fibroblasts, and the cell cycle of dermal cells were determined. In vitro study, the proliferation and apoptosis of fibroblasts from dermis were also detected. Results The thickness of dermal layer were reduced obviously in diabetic rat, with the atrophied, swollen and degenerated collagen fibers and a focal chronic inflammatory cells infiltration. The contents of glucose, AGEs in diabetic skin and the expression of PCNA were higher than those in the controls. In diabetic rat group, the dermal cells showed the higher percentage of S stage(35.31±5.807 vs 17.17±9.598, P<0.05) and the normal percentage of G2/M stages when compared with the control group. The levels of OHP synthesis of dermal fibroblast and apoptotic cells were not significantly different from those of the control. The proliferations rates of dermal fibroblasts were significantly lower than those in the control group(P<0.05 or 0.01) when the fibroblasts exposed to the high concentrations of glucose(5.5 mmol/L, and 25 mmol/L) and AGE-HSA(50,100,200,and 300 ug/ml) for 48h. The apoptotic rates of the fibroblasts were significantly higher than in control group (P<0.01) when cultured with 100, 200 or 300 ug/ml AGE-HSA and 25 mmol/L sugar for 48 h. The proliferation and apoptotic rates of the fibroblasts showed a dose dependent effect of AGE-HSA. Conclusions The high contents of dermal glucose and AGEs in diabetic rat skin have the inhibiting effects on dermal fibroblast, which might be one of the most important reasons leading to “underlying disorder” in diabetic skin and one of the most important mechanisms in the pathogenesis of refractory wound.