Lee M A, Palace J, Stabler G, Ford J, Gearing A, Miller K
Department of Clinical Neurology, The Radcliffe Infirmary, Oxford, UK.
Brain. 1999 Feb;122 ( Pt 2):191-7. doi: 10.1093/brain/122.2.191.
Metalloproteinases have been implicated in the pathogenesis of multiple sclerosis. We report longitudinal serum levels of gelatinase B and of the tissue inhibitors of matrix metalloproteinases (TIMP), TIMP-1 and TIMP-2, in 21 patients with relapsing multiple sclerosis. Patients had monthly clinical and gadolinium-enhanced MRI follow-up for 10 months. Longitudinal samples in nine healthy controls and cross-sectional samples from 12 patients with inflammatory CNS disease and 15 patients with other neurological diseases were used for comparison. Average serum gelatinase B, TIMP-1 and TIMP-2 levels were significantly higher in multiple sclerosis patients and those with other neurological diseases than in healthy controls. In the patients with multiple sclerosis, gelatinase B levels were significantly higher during clinical relapse compared with periods of clinical stability. Multiple sclerosis patients with high mean serum gelatinase B levels had significantly more T1-weighted gadolinium-enhancing MRI lesions than those with mean levels within the control range. TIMP-1 levels were not different during relapse and between relapses. There was a trend for TIMP-2 levels to be lower during relapse compared with non-relapse periods. For similar levels of serum gelatinase B, associated TIMP-1 levels were significantly lower and TIMP-2 levels significantly higher in multiple sclerosis patients compared with the inflammatory CNS control group. We propose that an abnormality in the inhibitory response to metalloproteinases may play an aetiological role in the chronicity of multiple sclerosis.
金属蛋白酶与多发性硬化症的发病机制有关。我们报告了21例复发型多发性硬化症患者血清中明胶酶B以及基质金属蛋白酶组织抑制剂（TIMP）-1和TIMP-2的纵向水平。患者接受了为期10个月的每月一次临床及钆增强磁共振成像（MRI）随访。选取9名健康对照者的纵向样本以及12例炎性中枢神经系统疾病患者和15例其他神经系统疾病患者的横断面样本用于比较。多发性硬化症患者以及其他神经系统疾病患者血清中明胶酶B、TIMP-1和TIMP-2的平均水平显著高于健康对照者。在多发性硬化症患者中，临床复发期的明胶酶B水平显著高于临床稳定期。平均血清明胶酶B水平较高的多发性硬化症患者，其T1加权钆增强MRI病灶显著多于平均水平在对照范围内的患者。TIMP-1水平在复发期和非复发期无差异。复发期TIMP-2水平有低于非复发期的趋势。与炎性中枢神经系统疾病对照组相比，在血清明胶酶B水平相似的情况下，多发性硬化症患者的相关TIMP-1水平显著较低，TIMP-2水平显著较高。我们认为，对金属蛋白酶抑制反应的异常可能在多发性硬化症的慢性化过程中起病因学作用。
