Acute Effects of Haemodialysis on Pro-/Anti-Apoptotic Genes in Peripheral Blood Leukocytes
Acute Effects of Haemodialysis on Pro-/Anti-Apoptotic Genes in Peripheral Blood Leukocytes
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DOI：
10.1159/000185486
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发表时间：
2008-01-01
影响因子：
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通讯作者：
Alexander, Dorothea
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文献类型：
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作者：
Friedrich, Bjoern;Janessa, Andrea;Alexander, Dorothea
一些研究表明，ESRD患者存在显著的功能失调的凋亡状态和/或反应。先前发表的研究对血液透析（HD）治疗对凋亡基因上调或下调的急性影响存在争议。28例慢性HD患者使用高通量膜4008透析器进行4小时血液透析。在亚组分析中，将患者分为低（0.5 mg/dl）和高（0.5 ~ 5.0 mg/dl） CRP组。在HD开始前和开始后240分钟抽血。利用实时荧光定量PCR分析了从血液白细胞中立即分离的RNA中编码促凋亡或抗凋亡基因的转录物水平的急性变化。在本研究中，我们检测到HD期间死亡受体CD95/Fas（诱导因子（IF） 1.55 +/- 0.16）、死亡受体5 (DR5) （IF 1.17 +/- 0.08）和caspase 8 （IF 1.37 +/- 0.14）基因表达显著升高。HD处理后，caspase 5和抗凋亡Bcl-2家族成员（如Bcl-2和bcl - 2l2）的CD95L （TRAIL）配体mRNA水平略有升高，但不显著。另一种抗凋亡分子BAG3在HD后被诱导（IF为1.16 +/- 0.07）。除了作为免疫细胞的激活剂，CD40L已被证明在HD治疗后被强烈诱导（IF 1.70 +/- 0.20）。亚组分析显示低与高CRP患者组或糖尿病与非糖尿病患者组之间无显著差异。这些结果表明，常规血液透析治疗对促凋亡和抗凋亡分子的转录有显著影响，并通过激活死亡受体和启动物caspase 8参与凋亡的外部途径。此外，透析后淋巴细胞似乎被CD40L激活，CD40L是一种早期t细胞激活标志物。版权所有(c) 2008 S. Karger AG，巴塞尔
Several studies have implicated a remarkable dysfunctional apoptotic state and/or response in ESRD patients. Previously published studies are controversial with respect to acute effects of haemodialysis (HD) treatment on up- or downregulation of apoptotic genes. Twenty-eight chronic HD patients were haemodialysed for 4 hours with a 4008 dialyser using high-flux membranes. For subgroup analysis, patients were separated into a low (up to 0.5 mg/dl) and a high (0.5 to 5.0 mg/dl) CRP group. Blood was drawn prior to HD and 240 min after initiation of HD. Acute changes of transcript levels encoding pro- or anti-apoptotic genes were analyzed in RNA immediately isolated from blood leukocytes using quantitative real-time PCR. In the present study, we detected a significant elevation of the death receptor CD95/Fas (induction factor (IF) 1.55 +/- 0.16), the death receptor 5 (DR5) (IF 1.17 +/- 0.08), and caspase 8 (IF 1.37 +/- 0.14) gene expression during HD. mRNA levels of the respective ligands CD95L, TRAIL), of the caspase 5 and anti-apoptotic Bcl-2 family members such as Bcl-2 and Bcl2l2 were slightly, but not significantly, increased after HD treatment. An additional anti-apoptotic molecule, BAG3, was found to be slightly, but significantly, induced after HD (IF 1.16 +/- 0.07). In addition to being an activator of immune cells, CD40L has been shown to be strongly induced after HD treatment (IF 1.70 +/- 0.20). Subgroup analysis revealed no significant differences between low vs. high CRP patient groups or diabetic vs. non-diabetic patients. These results indicate a marked influence of routine haemodialysis treatment on the transcription of pro- and antiapoptotic molecules and the involvement of the extrinsic pathway for apoptosis through the activation of death receptors and the initiator caspase 8. Furthermore, following dialysis, lymphocytes seem to be activated by CD40L, which represents an early T-cell activation marker. Copyright (c) 2008 S. Karger AG, Basel