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首页> 外文期刊>Cellular Physiology and Biochemistry >Acute Effects of Haemodialysis on Pro-/Anti-Apoptotic Genes in Peripheral Blood Leukocytes
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Acute Effects of Haemodialysis on Pro-/Anti-Apoptotic Genes in Peripheral Blood Leukocytes

机译：血液透析对外周血白细胞中促/抗凋亡基因的急性影响

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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.
机译：多项研究表明，ESRD患者的凋亡状态和/或反应异常显着。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引起争议。使用高通量膜在4008透析仪中对28名慢性HD患者进行了4小时的血液透析。对于亚组分析，将患者分为低（最高0.5 mg / dl）和高（0.5至5.0 mg / dl）CRP组。 HD开始前和HD开始后240分钟抽血。使用定量实时PCR在从血液白细胞立即分离的RNA中分析了编码促凋亡或抗凋亡基因的转录水平的急性变化。在本研究中，我们检测到死亡受体CD95 / Fas（诱导因子（IF）1.55 +/- 0.16），死亡受体5（DR5）（IF 1.17 +/- 0.08）和胱天蛋白酶8（ HD期间IF 1.37 +/- 0.14）基因表达。在HD处理后，半胱天冬酶5和抗凋亡的Bcl-2家族成员（如Bcl-2和Bcl2l2）的各个配体CD95L，TRAIL）的mRNA水平略有升高，但不明显。发现在HD（IF 1.16 +/- 0.07）后，另一种抗凋亡分子BAG3被轻微但显着诱导。除了是免疫细胞的激活剂，CD40L还被证明在HD治疗后被强烈诱导（IF 1.70 +/- 0.20）。亚组分析显示，低CRP组和高CRP组或糖尿病组和非糖尿病组之间无显着差异。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以及通过激活死亡受体和引发剂胱天蛋白酶8激活凋亡的外在途径的影响。此外，在透析后，淋巴细胞似乎被激活了。 CD40L代表早期的T细胞活化标记。

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