维持性血液透析慢性肾衰竭患者皮肤中凋亡调节蛋白p53和Bcl-2的表达

Expression of apoptosis regulatory proteins p53 and Bcl-2 in skin of patients with chronic renal failure on maintenance haemodialysis.

作者信息

El-Domyati M M, Ahmad H M, Nagy I, Zahran A

机构信息

Department of Dermatology, Faculty of Medicine, Al-Minya University, Al-Minya, Egypt.

出版信息

J Eur Acad Dermatol Venereol. 2007 Jul;21(6):795-801. doi: 10.1111/j.1468-3083.2006.02090.x.

DOI:10.1111/j.1468-3083.2006.02090.x

PMID:17567310

Abstract

BACKGROUND

Chronic renal failure results in multi-organ system derangement including cardiovascular, gastrointestinal, neurological, endocrinal, blood and dermatological abnormalities. Maintenance of skin homeostasis requires a delicate balance between proliferation, differentiation and apoptosis. p53 and Bcl-2 proteins play a central role in the regulation of apoptosis.

OBJECTIVE

Evaluation of the expression of apoptosis regulatory proteins p53 and Bcl-2 in apparently normal skin of patients, with chronic renal failure on maintenance haemodialysis, with respect to their role in the apoptotic process.

METHODS

Biopsy specimens were obtained from 10 patients with chronic renal failure on maintenance haemodialysis, as well as seven age-matched control subjects. Computer-assisted image analysis was employed to measure epidermal thickness in H&E-stained sections. Immunoperoxidase technique was also used to demonstrate p53 and Bcl-2 proteins and the TUNEL technique for detection of apoptotic cells in these specimens.

RESULTS

The mean epidermal thickness was significantly higher (P < 0.0001) in patients than controls. Meanwhile, no apoptotic cells were detected in the epidermis of patients. On the other hand, a statistically significant difference was observed in both p53 (P = 0.0001) and Bcl-2 expression (P = 0.0003) when comparing patients and controls. Expression of p53 (2.74 +/- 0.84) and Bcl-2 (3.45 +/- 1.35) proteins was higher in skin samples obtained from patients with chronic renal failure and on maintenance haemodialysis than those from control cases (0.5 +/- 0.96 and 0.8 +/- 0.6, respectively). Moreover, Bcl-2 expression in patients was observed in basal as well as squamous cell layers of skin, whereas in control subjects it was confined to the basal cell layer only.

CONCLUSION

These findings suggest that an alteration in the proliferation/apoptosis balance may be present in the skin of such patients.

摘要

背景

慢性肾衰竭会导致多器官系统紊乱，包括心血管、胃肠道、神经、内分泌、血液及皮肤异常。维持皮肤内环境稳定需要细胞增殖、分化和凋亡之间的微妙平衡。p53和Bcl-2蛋白在细胞凋亡调控中起核心作用。

目的

评估维持性血液透析的慢性肾衰竭患者外观正常皮肤中凋亡调节蛋白p53和Bcl-2的表达情况及其在凋亡过程中的作用。

方法

从10例维持性血液透析的慢性肾衰竭患者以及7例年龄匹配的对照者身上获取活检标本。采用计算机辅助图像分析技术测量苏木精-伊红染色切片中的表皮厚度。免疫过氧化物酶技术用于检测p53和Bcl-2蛋白，TUNEL技术用于检测这些标本中的凋亡细胞。

结果

患者的平均表皮厚度显著高于对照组（P < 0.0001）。同时，在患者的表皮中未检测到凋亡细胞。另一方面，比较患者和对照组时，p53（P = 0.0001）和Bcl-2表达（P = 0.0003）均存在统计学显著差异。慢性肾衰竭维持性血液透析患者皮肤样本中p53（2.74 ± 0.84）和Bcl-2（3.45 ± 1.35）蛋白的表达高于对照病例（分别为0.5 ± 0.96和0.8 ± 0.6）。此外，患者皮肤的基底细胞层和鳞状细胞层均观察到Bcl-2表达，而对照组仅局限于基底细胞层。