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单纯性腹膜硬化中的肌成纤维细胞分化

Myofibroblastic differentiation in simple peritoneal sclerosis.

作者信息

Del Peso G, Jimenez-Heffernan J A, Bajo M A, Hevia C, Aguilera A, Castro M J, Sanchez-Tomero J A, Lopez-Cabrera M, Selgas R

机构信息

Department of Nephrology, University Hospital La Paz, Paseo de la Castellana 261, Madrid 28046, Spain.

出版信息

Int J Artif Organs. 2005 Feb;28(2):135-40. doi: 10.1177/039139880502800209.

DOI:10.1177/039139880502800209
PMID:15770601
Abstract

OBJECTIVE

To analyze the presence of myofibroblasts in a series of peritoneal dialysis (PD) patients with simple sclerosis and non-PD, uremic patients. Since there is a close correlation between active fibrosis and myofibroblastic differentiation we wanted to test if myofibroblasts are present in uremic, non-PD peritoneal samples. To determine if there are correlations between myofibroblastic presence and other functional and morphologic peritoneal parameters.

METHODS

Biopsies were collected from three patient groups: 1) Normal control samples (n = 15) of parietal and visceral peritoneum 2) non-PD uremic patients (n = 16); and 3) uremic patients on PD (n = 32). Peritoneal morphologic and functional parameters and immunohistochemical expression of alfa-smooth muscle actin was analyzed in each case. Vascular endothelial growth factor (VEGF), bcl-2 anti-apoptotic protein, and progesterone receptor was evaluated in a subset of cases.

RESULTS

Myofibroblasts were present in 56.3% of the patients with PD-related simple sclerosis. In most cases they were distributed in the upper submesothelial area. None of the biopsies from normal controls and uremic, non-PD patients showed myofibroblasts. Within the group of PD patients, myofibroblasts showed no correlation with time on dialysis, urea/creatinine MTAC, episodes of peritonitis, submesothelial thickening, hyalinizing vasculopathy or mesothelial status. In a subset of PD patients VEGF expression was observed in submesothelial fibroblastic cells. No expression of progesterone receptor or bcl-2 was observed.

CONCLUSIONS

Myofibroblasts are a reliable and simple indicator of fibrosis since they appear in early stages of PD treatment and in patients with minor morphologic anomalies. They are not exclusive of patients with sclerosing peritonitis, ultrafiltration loss or long standing treatment. Their absence in non-PD, uremic patients suggest that uremia-related fibrosis takes place without a significant participation of myofibroblasts.

摘要

目的

分析一系列患有单纯性硬化的腹膜透析(PD)患者以及非PD尿毒症患者中肌成纤维细胞的存在情况。由于活跃纤维化与肌成纤维细胞分化之间存在密切关联,我们想要检测尿毒症非PD腹膜样本中是否存在肌成纤维细胞。以确定肌成纤维细胞的存在与其他功能性和形态学腹膜参数之间是否存在相关性。

方法

从三组患者中获取活检样本:1)壁层和脏层腹膜的正常对照样本(n = 15);2)非PD尿毒症患者(n = 16);3)接受PD治疗的尿毒症患者(n = 32)。分析每种情况下的腹膜形态学和功能参数以及α-平滑肌肌动蛋白的免疫组化表达。在部分病例中评估血管内皮生长因子(VEGF)、bcl-2抗凋亡蛋白和孕激素受体。

结果

在56.3%的与PD相关的单纯性硬化患者中存在肌成纤维细胞。在大多数情况下,它们分布于上皮下区域。正常对照以及尿毒症非PD患者的活检样本均未显示有肌成纤维细胞。在PD患者组中,肌成纤维细胞与透析时间、尿素/肌酐转运面积系数(MTAC)、腹膜炎发作次数、上皮下增厚、玻璃样变血管病或间皮状态均无相关性。在部分PD患者中,观察到上皮下成纤维细胞中有VEGF表达。未观察到孕激素受体或bcl-2的表达。

结论

肌成纤维细胞是纤维化的一个可靠且简单的指标,因为它们出现在PD治疗的早期阶段以及形态学异常较小的患者中。它们并非仅见于硬化性腹膜炎、超滤丧失或长期治疗的患者。在非PD尿毒症患者中未发现肌成纤维细胞,这表明尿毒症相关纤维化的发生在很大程度上并非由肌成纤维细胞参与。

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