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长期腹膜透析治疗会引发与适应性免疫相关的基因激活。

Long-term peritoneal dialysis treatment provokes activation of genes related to adaptive immunity.

机构信息

Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

出版信息

Physiol Res. 2019 Oct 25;68(5):775-783. doi: 10.33549/physiolres.934158. Epub 2019 Aug 19.

DOI:10.33549/physiolres.934158
PMID:31424258
Abstract

Permanent irritation of the peritoneum during peritoneal dialysis (PD) treatment leads to local chronic inflammation and subsequently activation of processes driving fibrogenesis in the long-term. The aim of the study was to compare the peritoneal effluent transcriptome of 20 patients treated less and 13 patients treated more than 2 years using microarray analysis. An increased expression of genes associated with an immune response was observed in long-term treated patients with well preserved peritoneal function, when compared to patients treated less than 2 years. From 100 genes highly expressed in long-term patients, a significant up-regulation of six was found by RT-qPCR: LY9 (lymphocyte antigen 9), TNSFR4 (tumor necrosis factor receptor superfamily, member 4), CD 79A (CD79a molecule), CCR7 (chemokine C-C receptor 7), CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) and IL2RA (interleukin 2 receptor alpha chain). Furthermore, the effluent cell population was analysed. A positive relationship between the number of granulocytes and NK cells on one hand, and duration of PD treatment on the other, was shown. We conclude, that the mechanisms of adaptive immunity promoting T helper 2 cells response are activated in the long-term before functional alterations develop. It consequently might trigger the fibrosis promoting processes.

摘要

在腹膜透析 (PD) 治疗过程中,腹膜的持续刺激会导致局部慢性炎症,并随后在长期内激活促纤维化过程。本研究旨在通过微阵列分析比较接受治疗少于 2 年的 20 名患者和接受治疗超过 2 年的 13 名患者的腹膜流出物转录组。与治疗少于 2 年的患者相比,腹膜功能良好的长期治疗患者中观察到与免疫反应相关的基因表达增加。通过 RT-qPCR 发现,在长期治疗患者中高度表达的 100 个基因中,有 6 个基因显著上调:LY9(淋巴细胞抗原 9)、TNSFR4(肿瘤坏死因子受体超家族成员 4)、CD79A(CD79a 分子)、CCR7(趋化因子 C-C 受体 7)、CEACAM1(癌胚抗原相关细胞黏附分子 1)和 IL2RA(白细胞介素 2 受体α链)。此外,还分析了流出细胞群体。结果表明,一方面,粒细胞和 NK 细胞的数量与 PD 治疗的持续时间呈正相关。我们的结论是,在出现功能改变之前,长期刺激会激活适应性免疫促进 T 辅助 2 细胞反应的机制,从而可能引发纤维化促进过程。

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