Chinese Journal of Blood Purification ›› 2013, Vol. 12 ›› Issue (11): 581-585.doi: 10.3969/j.issn.1671-4091.2013.11.00

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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

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