Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis
Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis
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DOI：
10.1191/1352458502ms800oa
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发表时间：
2002-05-01
期刊：
影响因子：
--
通讯作者：
Riccio, P
中科院分区：
文献类型：
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作者：
Liuzzi, GM;Trojano, M;Riccio, P
采用酶谱法和酶联免疫吸附试验（ELISA）检测神经系统疾病患者血清和脑脊液（CSF）中基质金属蛋白酶9（MMP-9）。复发缓解型多发性硬化症（RR-MS）患者的血清和CSF MMP-9水平与炎性神经系统疾病（IND）患者相当，但高于非炎性神经系统疾病（NIND）患者和健康供体（HD）。活动期RR-MS中MMP-9的表达高于非活动期RR-MS，提示MS中MMP-9的表达与临床疾病活动有关。在IND和NIND中观察到CSF/血清白蛋白（Q（Alb））和CSF/血清MMP-9（Q（MMP-9））之间的相关性，但在RR-MS患者中未观察到，表明NIND和IND患者的CSF MMP-9水平可能受血清MMP-9和血脑屏障（BBB）通透性特性的影响。MS患者的Q（MMP-9）：Q（Alb）（MMP-9指数）值高于IND和NIND患者，这表明MS中CSF MMP-9的增加可能是由于MMP-9的鞘内合成。RR-MS患者血清MMP-9和TIMP-1水平呈负相关，提示MS患者血清MMP-9水平升高和TIMP-1水平降低均可能导致血脑屏障破坏和T淋巴细胞进入CNS。
Matrix metalloproteinase-9 (MMP-9) was detected by zymography and enzyme-linked immunosorbent assay (ELISA) in matched serum and cerebrospinal fluid (CSF) samples from patients with neurological diseases. Patients with relapsing-remitting multiple sclerosis (RR-MS) had serum and CSF MMP-9 levels comparable to those from patients with inflammatory neurological diseases (INDs), but higher than patients with non-inflammatory neurological diseases (NINDs) and healthy donors (HDs). MMP-9 increased in active RR-MS in comparison with inactive RR-MS implying that MMP-9 in MS is related with clinical disease activity. A correlation between the CSF/serum albumin (Q(Alb)) and CSF/serum MMP-9 (Q(MMP-9)) was observed in IND and NIND but not in RR-MS patients, indicating that CSF MMP-9 levels in NIND and IND patients could be influenced by serum MMP-9 and blood-brain barrier (BBB) permeability properties. MS patients had higher values of Q(MMP-9):Q(Alb) (MMP-9 index) than IND and NIND patients suggesting that in MS the increase in CSF MMP-9 could be due to intrathecal synthesis of MMP-9. A significant inverse correlation was found between MMP-9 and its endogenous inhibitor TIMP-1in RR-MS indicating that in MS patients both the increase in MMP-9 and the decrease in TIMP-1 serum levels could contribute to BBB disruption and T-lymphocyte entry into the CNS.