Elevated tumor necrosis factor-α in skeletal muscle after stroke
Elevated tumor necrosis factor-α in skeletal muscle after stroke
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DOI：
10.1161/01.str.0000177878.33559.fe
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发表时间：
2005-09-01
期刊：
影响因子：
8.3
通讯作者：
Macko, RF
中科院分区：
文献类型：
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作者：
Hafer-Macko, CE;Yu, SZ;Macko, RF
背景和目的-肿瘤坏死因子-α (TNF-α) 是一种在正常肌肉中表达可忽略不计的炎症细胞因子，在以肌肉萎缩和胰岛素抵抗为特征的特定代谢条件下会升高。炎症是中风发病机制的基础。中风患者患有严重的肌肉萎缩，并且糖尿病和胰岛素抵抗的患病率很高。然而，之前没有研究检查偏瘫骨骼肌中 TNF-α 的表达。本研究探讨慢性缺血性中风患者和年龄匹配对照的偏瘫腿部肌肉中 TNF-α mRNA 水平是否升高。方法 - 从 n = 20 名偏瘫中风患者和 n = 9 名健康对照的双侧股外侧肌活检中提取总 RNA，逆转录为 cDNA，然后实时扩增 TNF-α 转录本 定量聚合酶链反应。 TNF-α mRNA 浓度针对酸性核糖体磷蛋白（管家基因）进行标准化。结果 - 与对照腿部肌肉相比，瘫痪腿部肌肉的 TNF-α mRNA 水平高 2.8 倍（6.28 +/- 1.86 对比 2.28 +/- 0.67；P < 0.03），非瘫痪腿部肌肉的 TNF-α mRNA 水平高 1.6 倍（3.71 +/- 1.02；P < 0.11) 比较 带控件。与非瘫痪腿部相比，瘫痪腿部的 TNF-α mRNA 有较高的趋势。结论 - 研究结果表明，瘫痪腿部肌肉中 TNF-α 表达增加，表明中风肌肉中的炎症途径加速。进一步的研究正在进行中，以确定肌肉注射 TNF-α 是否会导致中风后的萎缩和代谢异常。
Background and Purpose - Tumor necrosis factor-alpha (TNF-alpha), an inflammatory cytokine negligibly expressed in normal muscle, is elevated in selected metabolic conditions characterized by muscle wasting and insulin resistance. Inflammation is fundamental to stroke pathogenesis. Stroke patients have gross muscular atrophy and high prevalence of diabetes and insulin resistance. Yet, no previous studies examined TNF-alpha expression in hemiparetic skeletal muscle. This study investigates whether TNF-alpha mRNA levels are elevated in paretic compared with nonparetic leg muscles of chronic ischemic stroke patients and age-matched controls.Method - Total RNA extracted from bilateral vastus lateralis muscle biopsies from n = 20 hemiparetic stroke patients and n = 9 healthy controls was reverse transcribed to cDNA, then TNF-alpha transcripts were amplified by real-time quantitative polymerase chain reaction. TNF-alpha mRNA concentrations were normalized against acidic ribosomal phosphoprotein, housekeeping gene.Results - TNF-alpha mRNA levels were 2.8-fold higher in paretic compared with control leg muscle (6.28 +/- 1.86 versus 2.28 +/- 0.67; P < 0.03) and 1.6-fold higher in nonparetic leg (3.71 +/- 1.02; P < 0.11) compared with controls. There was a trend for higher TNF-alpha mRNA in paretic compared with nonparetic leg.Conclusions - Findings demonstrate increased TNF-alpha expression in paretic leg muscle, suggesting inflammatory pathways are accelerated in stroke muscle. Further studies are under way to determine whether intramuscular TNF-alpha contributes to atrophy and metabolic abnormalities after stroke.