Neuromuscular Unit, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
Eur J Neurol. 2010 Feb;17(2):226-31. doi: 10.1111/j.1468-1331.2009.02775.x. Epub 2009 Oct 1.
Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). We investigated the expression of MMPs and tissue inhibitors of matrix metalloproteinases (TIMPs) in serum and cerebrospinal fluid (CSF) correlating the results with age, disease duration and the clinical course.
The material consisted of 30 ALS patients and 15 age-matched healthy controls. ELISA method to determine the expression of MT-MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 in serum and CSF was used. MMP-2 and MMP-9 by zymography was also tested.
In serum MT-MMP-1, MMP-2, MMP-9 and TIMP-1 expression was increased, especially in mild ALS cases. TIMP-2 values were normal. In CSF MT-MMP-1, MMP-2 and TIMP-1 level was either increased or normal, that of MMP-9 was decreased. TIMP-2 did not change. No correlation of MMPs and TIMP-1 expression in serum and CSF and the age of the patients was found. A correlation was observed between MMPs and TIMPs and disease duration.
Increased level of MMPs and TIMP-1 of ALS patients may reflect the degeneration process of motor neurons and skeletal muscles and/or is associated with tissues remodeling. The low level of MMP-9 in CSF may result from impaired balance between MMP-9 and TIMP-1 and/or its increased intrathecal degradation and physical clearance. Although the role of changed MMPs/TIMPs level in the pathogenesis of ALS is not clear their analysis in serum may be used as prognostic factor and a potential marker for monitoring treatment effects.
基质金属蛋白酶（MMPs）参与肌萎缩侧索硬化症（ALS）运动神经元退行性变的发病机制。我们研究了 MMPs 和基质金属蛋白酶组织抑制剂（TIMPs）在血清和脑脊液（CSF）中的表达，将结果与年龄、疾病持续时间和临床病程相关联。
该材料包括 30 名 ALS 患者和 15 名年龄匹配的健康对照者。采用 ELISA 法测定血清和 CSF 中 MT-MMP-1、MMP-2、MMP-9、TIMP-1 和 TIMP-2 的表达，同时还通过酶谱法检测 MMP-2 和 MMP-9。
血清 MT-MMP-1、MMP-2、MMP-9 和 TIMP-1 的表达增加，尤其是在轻度 ALS 病例中。TIMP-2 值正常。CSF 中 MT-MMP-1、MMP-2 和 TIMP-1 水平升高或正常，MMP-9 水平降低。TIMP-2 没有变化。未发现血清和 CSF 中 MMPs 和 TIMP-1 的表达与患者年龄之间存在相关性。观察到 MMPs 和 TIMPs 与疾病持续时间之间存在相关性。
ALS 患者 MMPs 和 TIMP-1 水平升高可能反映运动神经元和骨骼肌的退行性变过程，或与组织重塑有关。CSF 中 MMP-9 水平降低可能是由于 MMP-9 和 TIMP-1 之间平衡受损，以及其在鞘内的降解和物理清除增加所致。尽管改变的 MMPs/TIMPs 水平在 ALS 发病机制中的作用尚不清楚，但对其进行分析可能有助于作为预后因素和监测治疗效果的潜在标志物。
