王建敏,甘华,王行"/>
不同血液净化方式终末期肾病患者血清对体外巨噬细胞ABCA1表达的影响
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重庆市卫生局重点项目(2010-1-6),国家科技支撑计划(2011BAI10B01).


Effect of serum of end stage renal disease patients undergoing different types of blood purification on ABCA1 expression in macrophages
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Supported by Key Project of Chongqing Health Bureau(2010-1-6) and the National Science and Technology Supporting Program of China(2011BAI10B01).

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    摘要:

    目的观察终末期肾病维持性透析(MHD)患者血清对巨噬细胞ATP结合盒转运子A1(ABCA1)表达的影响,并探讨不同血液净化方式对其的干预作用。方法采集血液透析(HD)患者(n=23)、血液透析滤过(HDF)患者(n=17)和健康对照者(n=23)空腹静脉血并制备血清。全自动生化分析仪测量血脂与hs-CRP水平,ELISA法检测血清TNF-α、单核细胞趋化蛋白1(MCP-1)、IL-6水平。将血清与THP-1源巨噬细胞共培养,RT-PCR检测ABCA1 mRNA表达,蛋白质印迹法检测ABCA1、STAT3、p-STAT3 蛋白表达。结果MHD患者血高密度脂蛋白胆固醇(HDL-c)、载脂蛋白A-Ⅰ(ApoA-Ⅰ)低于对照组(P<0.05), hs-CRP、TNF-α、MCP-1、IL-6高于对照组(P均<0.05)。HD治疗前及HDF治疗前患者血清干预的巨噬细胞ABCA1、STAT3及p-STAT3水平差异无统计学意义,但两组ABCA1水平均低于对照组(P<0.05),STAT3及p-STAT3水平与对照组比较差异无统计学意义。HD治疗后与HD治疗前相比,ABCA1、STAT3及p-STAT3水平差异无统计学意义;HDF治疗后与HDF治疗前及HD治疗后比较,ABCA1、STAT3及p-STAT3水平上升,差异有统计学意义(P<0.05)。结论HDF治疗较HD更能上调巨噬细胞ABCA1表达,增强其抗炎、促胆固醇流出作用,其作用机制可能与激活STAT3信号通路有关。

    Abstract:

    Objective To observe the effect of serum of end stage renal disease patients undergoing maintenance hemodialysis (MHD) on the expression of ATP-binding cassette transporter A1 (ABCA1) in macrophages, and to study the interventional effects of different types of blood purification on the effect of serum. MethodsTotally 40 MHD patients were divided into hemodialysis (HD) group (n=23) and hemodiafiltration (HDF) group (n=17), and 23 healthy people were taken as controls. THP-1 macrophages were incubated with sera of subjects from each group. The serum lipid profiles and hs-CRP were measured by automatic biochemical analyzer. The serum levels of TNF-α, monocyte chemotactic protein 1 (MCP-1) and IL-6 were measured by ELISA. The mRNA expression of ABCA1 in macrophage was examined by RT-PCR. Western blotting analysis was used to measure protein expression of ABCA1,STAT3 and p-STAT3 in THP-1 macrophages. Results The levels of high-density lipoprotein cholesterol (HDL-c) and apolipoproteinAⅠ (ApoA-Ⅰ) in patients with end stage renal disease were significantly lower, and those of hs-CPR, TNF-α, MCP-1,and IL-6 were significantly higher than those in healthy group (P<0.05).The expressions of ABCA1, STAT3 and p-STAT3 in macrophages were not significantly different before treatment with HD and HDF, but the levels of ABCA1 in HD group and HDF group were significantly lower than those in healthy control group (P<0.05).The levels of ABCA1, STAT3 and p-STAT3 were not significantly changed before and after treatment in HD group. In contrast, the levels of ABCA1, STAT3 and p-STAT3 were significantly increased after treatment in HDF group(P<0.05). Conclusion HDF is more potent than HD in up-regulating ABCA1 in macrophages of MHD patients, enhancing its anti-inflammation and inducing cholesterol efflux, and the mechanism might be related to the activation of STAT3 signaling pathway.

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  • 收稿日期:2012-07-09
  • 最后修改日期:2012-09-04
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  • 在线发布日期: 2012-11-22
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