终末期肾病患者外周血单个核细胞瘦素受体mRNA的表达及其与细胞因子水平的关系

齐华林; 江薇; 马骏; 许晨; 李素; 严海东

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中国血液净化 ›› 2006, Vol. 5 ›› Issue (3) : 141-144.

基础研究

终末期肾病患者外周血单个核细胞瘦素受体mRNA的表达及其与细胞因子水平的关系

1齐华林 1 江薇 2马骏 2许晨 2李素 1严海东

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摘要

目的探讨终末期肾病（ESRD）患者外周血单个核细胞（PBMC）表面2种瘦素(leptin) 受体（Ob-R）信使核糖核苷酸（mRNA）的表达及其与循环中leptin和肿瘤坏死因子-a水平（TNF-a）的关系，以及血液透析患者高细胞因子血症的可能发生机制。方法选择同济大学附属东方医院肾内科ESRD患者20例（其中维持性血液透析亚组12例，非透析亚组8例）和正常人10例，检测其血浆leptin和TNF-a水平；用RT-PCR方法检测PBMC表面两种leptin受体：长型受体(Ob-Rb)和短型受体(Ob-Ra)的相对表达水平。结果 ESRD患者血浆leptin、TNF-a水平明显高于正常人群(P＜0.01；P＜0.05),但血液透析亚组和非透析亚组两者之间差异无显著性。ESRD患者血液透析亚组和非透析亚组血浆leptin水平均与TNF-a呈正相关(r=0.688，P ＜0.05；r=0.801，P＜0.001)。所有研究对象PBM C均有Ob-Ra和Ob-Rb mRNA的表达，而Ob-Ra的平均表达水平约为Ob-Rb的7倍（P＜0.001)。ESRD患者Ob-Ra和Ob-RbmRNA的表达均高于正常对照组（P＜0.001)。ESRD患者血浆leptin、TNF-α水平与Ob-Ra mRNA、Ob-Rb mRNA的相对表达量呈显著的正相关（P＜0.05）。结论 ESRD患者外周血PBMC表面两种leptin受体表达水平均增高，其中Ob-Ra占优势；leptin水平与促炎症因子的关系值得进一步研究。

Abstract

Objective To elucidate the relationship between the expression leptin of receptors mRNA the surface of peripheral blood mononuclear cells and the plasma levels of leptin and tumor nocrosis factor a (TNF-a), and the cause of high plasma levels of proinflammatory cytokines in patients with end-stage renal disease(ESRD). Methods Human peripheral blood mononuclear cells were isolated from 20 ESRD patients(12 of them underwent hemodialysis and 8 of them did not) and 10 healthy controls. The levels of plasma leptin and TNF- a were measured. The relative expression levels of the 2 major leptin receptor splice variants, the long form (Ob-Rb) and the short form (Ob-Ra) in peripheral blood mononuclear cells，were measured by semi-quantitative reverse transcript polymerase chain reaction (RT-PCR).Results Plasma leptin and TNF-a levels were much higher in ESRD group than those in control group. However there was no significant difference between hemodialysis sub-group and non-dialysis sub-group. Plasma leptin levels were significantly correlated with BMI and FAT% in all subjects and with plasma TNF-a levels only in hemodialysis sub-group （r=0.688，P＜0.05）and non-dialysis sub-group (r=0.801，P＜0.001).But there was no,correlation in normal control group. Both Ob-Ra and Ob-Rb were coexpressed in all mRNAs tested. However, the expression level of the short form (Ob-Ra) was 7-fold higher on average than that level of the long form (Ob-Rb)(P＜0.001). The predominance of the short splice variant over the long one was apparent in all samples. The relative expression levels of Ob-Rb mRNA and Ob-Ra mRNA in ESRD were respectively higher than those in control group(P＜0.001, P＜0.001). Plasma leptin and TNF-a levels were significantly correlated with the relative expression levels of Ob-Ra mRNA and Ob-Rb mRNA in hemodialysis sub-group and non-dialysis sub-group.Conclusion Both Ob-Ra and Ob-Rb were coexpressed on the surface of peripheral blood mononuclear cells in ESRD patients. Short form receptor of leptin (Ob-Ra is predominent in all samples. Their relative expression levels are higher than those in healthy controls.The relationaship between hyperleptinemia and proinflammatory cytokines is to be investigated.