中国血液净化

中国血液净化 ›› 2013, Vol. 12 ›› Issue (11): 581-585.doi: 10.3969/j.issn.1671-4091.2013.11.00

• 临床研究 •    下一篇

炎症因子TNF-α/IL-6对透析患者骨骼肌消耗及myostatin和Atrogin-1表达的影响

  

  1. 1. 上海解放军第四五五医院
    2. 解放军第四五五医院
    3. 解放军第四五五医院 南京军区肾病研究所
  • 收稿日期:2013-05-30 修回日期:2013-07-15 出版日期:2013-11-12 发布日期:2013-11-12
  • 通讯作者: 王会玲 viollla@163.com E-mail:viollla@163.com
  • 基金资助:

    上海启明星跟踪基金(No.07QH14020)；上海浦江人才基金(10PJD016)

Inflammatory cytokine TNF-α/IL-6 related to muscle wasting and up-regulated expression of myostatin and Atrogin-1 in hemodialysis patients

  • Received:2013-05-30 Revised:2013-07-15 Online:2013-11-12 Published:2013-11-12
  • Supported by:

    Shanghai Qimingxing Grant

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摘要： 目的 研究血液透析患者骨骼肌消耗状态与炎症因子水平的内在关系和机制。方法 选择维持性血液透析患者(HD组)42例，以30例健康人群为正常对照组(Ctl)。主观全面营养评价法（SGA）法评估患者营养状态，采集人体测量学数据，收集临床生化指标，Elisa方法检测C-反应蛋白（CRP）、白介素－6（interleukin-6, IL-6）、肿瘤坏死因子-α（tumor necrosis factor alpha, TNF-α）等炎症因子水平；留取6位透析患者骨骼肌标本，与4位年龄性别匹配的非肾病者为对照，行HE染色并光镜下观察肌纤维形态，测量和分析直径肌纤维。荧光定量PCR检测肌萎缩标志分子myostatin、Atrogin-1及炎症因子的转录水平。结果 HD组患者的体重及BMI低于健康对照组，其血尿素氮、肌酐和尿酸水平明显升高，并伴轻度贫血，其血清总蛋白和白蛋白、转铁蛋白等营养指标虽然在正常范围，但较对照组明显降低，血脂、血糖与对照组比较无差异；HD组的CRP、TNF-α和IL-6等炎症因子水平显著升高p<0.05~0.01)；光镜下肌纤维形态较纤细、萎缩，肌束间隙较宽，肌纤维直径降低；荧光定量PCR检测结果显示透析患者肌肉组织的myostatin mRNA转录水平上调5.96倍，Atrogin-1 mRNA上调2.43倍；同时TNF-α和IL-6mRNA转录水平分别上调8.37倍和3.36倍。结论 血透患者骨骼肌消耗性营养不良与炎症因子水平升高相关；肌肉组织的TNF-α、IL-6表达上调，激活 myostatin和Atrogin-1的转录，可能是引起骨骼肌消耗的重要机制。

关键词: 透析, 营养不良, 炎症因子, 肌肉

Abstract: Objective Although a lot of research confirmed elevated systemic inflammation related to malnutrition in advanced chronic kidney disease (CKD), few clinic research revealed the mechanism of inflammatory cytokines impacted muscle wasting in patients with CKD. This study investigates the serum cytokines level and muscle wasting of patients with underlying maintenance hemodialysis (HD) and the expression of genes involved in the regulation of muscle atrophy. mass and that for the inflammatory cytokine TNF-α /IL-6 in muscle biopsies. Methods HD patients were selected according to the enrolled standard as HD group, 30 healthy adults with gender and age matched as control（Ctl）. We collected the biochemical and anthropometry data, measured inflammatory cytokine such as C-reactive protein( CRP), interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α) by ELISA with their serum samples. Then we got muscle sample from 6 HD patients and 4 non-HD patients, observed the muscle histology by light scope after HE staining, and analyzed the transcriptional levels of myostatin and Atrogin-1, TNF-α and IL-6 by real-time PCR. Results 42 patients enrolled in the study. The HD patients showed lower body weight and body mass index, the plasma total protein, albumin level and pre-albumin showed lower though still kept in normal limits. Also, HD had an abnormal renal function ( elevated of BUN, Serum creatinin and urea acid), slightly anemia, and higher levels of serum inflammatory cytokines such as CRP, TNF-α and IL-6(p<0.05~0.01). The morphologic observation showed muscle fibers were tenuous and atrophy in an extent, the space between fibers was widen. The muscle fiber diameter was decreased compared with Ctl. Interestingly, the muscle myostatin and Atrogin-1 mRNA levels was elevated 5.96 fold and 2.43 fold respectively; and the TNF-α, Il-6 mRNA increased 8.37 fold and 3.36 fold respectively measured by RT-PCR. Conclusions CKD patients underlying hemodialysis present elevated inflammatory cytokines level and obviously muscle wasting. Up-regulation of TNF-α and IL-6 expression, stimulating the transcription of myostatin and Atrogin-1, might be an important mechanism of muscle wasting in CKD.

Key words: hemodialysis, malnutrition, inflammatory cytokine, muscle