Ljubisavljevic Srdjan, Stojanovic I, Basic J, Vojinovic S, Stojanov D, Djordjevic G, Pavlovic D
Clinic of Neurology, Clinical Center Nis, Bul. Dr Zorana Djindjica 48, 18000, Nis, Serbia.
Institute for Pathophysiology, Faculty of Medicine, University of Nis, Bul. Dr Zorana Djindjica 81, 18000, Nis, Serbia.
J Mol Neurosci. 2015 Aug;56(4):840-847. doi: 10.1007/s12031-015-0521-x. Epub 2015 Feb 22.
Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in a variety of physiological and pathological processes, including those in CNS. In this study, plasma values of MMP-3 and MMP-9 have been compared in clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS) patients during their acute attacks, in relation to the biological activity of disease. Therefore, we compared the MMPs plasma values regarding Expanded Disability Status Scale (EDSS), progression index of disease (PID), acute brain lesion volume seen on magnetic resonance imaging (MRI) and index of blood-brain barrier (BBB) permeability destruction. The obtained results demonstrated higher plasma values of MMPs in both study groups than control values (p < 0.05). No statistical significances have been detected comparing the obtained values of both enzymes between CIS and RRMS group (p > 0.05). In both CIS and RRMS groups, the patients with higher EDSS showed higher MMPs plasma values (p < 0.05). The MMPs values were also significantly higher in both study patients with higher total number comparing to those with lower number of MRI brain lesion (p < 0.05) (beyond MMP-3 in RRMS). All obtained correlations, between MMPs and EDSS, PID, volume of MRI Gd-enhancement brain lesions, and index of BBB permeability, were positive (p < 0.05.) This study demonstrates alterations of both tested MMPs with closed correlation with the disease biological activity. Although MMPs are being implicated in the pathogenesis of acute neuroinflammation, the MMPs modulation might be useful in the future design of disease modifying therapy with the specific target profile.
基质金属蛋白酶（MMPs）是一类蛋白水解酶，参与多种生理和病理过程，包括中枢神经系统中的相关过程。在本研究中，对临床孤立综合征（CIS）和复发缓解型多发性硬化症（RRMS）患者急性发作期间血浆中MMP-3和MMP-9的值进行了比较，以探讨其与疾病生物学活性的关系。因此，我们比较了两组患者血浆中MMPs的值，同时分析了扩展残疾状态量表（EDSS）、疾病进展指数（PID）、磁共振成像（MRI）上显示的急性脑病变体积以及血脑屏障（BBB）通透性破坏指数。结果表明，两个研究组的MMPs血浆值均高于对照组（p < 0.05）。比较CIS组和RRMS组两种酶的测定值，未发现统计学差异（p > 0.05）。在CIS组和RRMS组中，EDSS评分较高的患者MMPs血浆值也较高（p < 0.05）。与MRI脑病变数量较少的患者相比，MRI脑病变总数较多的患者MMPs值也显著更高（p < 0.05）（RRMS组中MMP-3除外）。MMPs与EDSS、PID、MRI钆增强脑病变体积和BBB通透性指数之间的所有相关性均为正相关（p < 0.05）。本研究表明，所检测的两种MMPs均发生改变，且与疾病生物学活性密切相关。尽管MMPs参与了急性神经炎症的发病机制，但MMPs调节可能有助于未来设计具有特定靶点的疾病修饰疗法。
