Enhanced platelet apoptosis in chronic uremic patients
Enhanced platelet apoptosis in chronic uremic patients
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慢性尿毒症患者血小板凋亡增强
DOI：
10.3109/0886022x.2014.899473
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发表时间：
2014-07-01
期刊：
影响因子：
3
通讯作者：
Dai, Kesheng
中科院分区：
文献类型：
--
作者：
Li, Ming;Wang, Zhaoyue;Dai, Kesheng
摘要背景：关于尿毒症患者血小板凋亡及其对血小板功能障碍的作用的研究还很少。本研究旨在分析接受不同透析方式的尿毒症患者的血小板凋亡。方法：16例慢性尿毒症患者（5例血液透析，6例腹膜透析，5例非透析）和16例对照者。通过流式细胞术或Western-Blot检测富血小板血浆中的凋亡事件，包括线粒体内膜电位（Δ μ m）的去极化、磷脂酰丝氨酸（PS）暴露、caspase-3和Bcl-2家族蛋白的激活变化。将洗涤后的正常血小板与正常或尿毒症贫血小板血浆孵育，然后检测凋亡事件。用瑞斯托康诱导的血小板聚集功能试验评价血小板功能。结果如下：与对照组相比，尿毒症血小板表现出更大的凋亡，对于Δ λ m去极化（43.48 ± 9.58 vs. 52.76 ± 15.36，p = 0.005）以及PS暴露（1.36 ± 0.51 vs. 0.99 ± 0.27，p < 0.001）。不同治疗组之间无显著差异（对于ΔΨm去极化，f = 0.16，p = 0.85;对于PS暴露，f = 1.06，p = 0.36）。Western Blot分析显示caspase-3活化和促凋亡Bcl-2家族蛋白表达。血小板暴露于尿毒症血浆中表现出明显的凋亡现象。在尿毒症患者和经治疗的血小板中，利托那肽诱导的血小板聚集显著减少。结论：尿毒症患者血小板存在凋亡。尿毒症血浆加速正常血小板的凋亡，导致尿毒症患者血小板功能障碍。尿毒症血小板凋亡与透析方式无关。
Abstract Background: There is a paucity of research on platelet apoptosis and its contribution to platelet dysfunction in uremic patients. The present study sought to analyze platelets apoptosis in uremic patients who underwent different dialysis modalities. Methods: Sixteen chronic uremic patients (5 on hemodialysis, 6 on peritoneal dialysis and 5 on non-dialysis) and 16 controls were studied. Platelet-rich plasma was detected for apoptotic events including depolarization of mitochondrial inner membrane potential (ΔΨm), phosphatidylserine (PS) exposure, activation of caspases-3 and Bcl-2 family proteins variations by Flow Cytometry or by Western-Blot. Washed normal platelets were incubated with normal or uremic platelet poor plasma and then were detected apoptotic events. Platelets function was assessed by ristocetin induced aggregative function test. Results: Compared to controls, uremic platelets demonstrated greater apoptosis for the ΔΨm depolarization (43.48 ± 9.58 vs. 52.76 ± 15.36, p = 0.005) as well as PS exposure (1.36 ± 0.51 vs. 0.99 ± 0.27, p < 0.001). There was no significant difference among different treatment groups (for the ΔΨm depolarization f = 0.16, p = 0.85; for the PS exposure f = 1.06, p = 0.36). Western Blot analyses showed caspase-3 activation and pro-apoptotic Bcl-2 family proteins expression. Platelets exposed to uremic plasma exhibited distinct apoptosis phenomena. Ristocetin induced platelet aggregation was markedly diminished in uremic patients and treated platelets. Conclusions: These findings indicate that platelets are incurred apoptosis in uremia patients. Uremic plasma accelerates apoptosis of normal platelets, resulting in a dysfunctional pattern of platelets in uremia. Uremic platelets apoptosis has no relationship with dialysis modality.